BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of"mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase"in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.

Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective:To systematically evaluate the efficacy, patient-reported outcomes (PROs) and safety of hyaluronic acid (HA) fillers and collagen stimulators (PCL/PLLA) for various facial aesthetic indications.Methods:This study focused on facial fillers approved and widely used in China, including HA fillers such as Juvéderm?, Restylane?, Belotero?, Fillmed?, and PCL/PLLA such as Ellansé?, L?viselle?, and CureWhite?. A systematic literature search was conducted across both English and Chinese databases, including PubMed, Cochrane Library, Embase, CNKI, and Wanfang Data, covering the period from database inception to August 24, 2023, to identify randomized controlled trials (RCTs). The characteristics and outcomes of the included RCTs were summarized and analyzed, including efficacy indicators by injection site, patient satisfaction, and safety profiles. Network meta-analysis (NMA) was performed using R software to compare efficacy outcomes, including the 6-month improvement response rate for nasolabial folds (NLF) and the global aesthetic improvement scale (GAIS).Results:A total of 38 articles were included. Among them, Juvéderm? was most frequently used as the treatment group (17 out of 38 articles), while Restylane? was the most common comparator (17 out of 38 articles), particularly in studies involving NLF injections (15 out of 16 articles). For collagen stimulators, only 2 studies on Ellansé? were included, both focusing solely on NLF treatment. Quality assessment showed that 34 studies were of medium to high quality, with Juvéderm? accounting for the majority of high-quality studies (11 articles). Based on injection sites, NLF was the most studied area (16 articles), followed by the midface (8 articles), and the remaining 14 articles covered other regions including lips, nose, chin, and infraorbital area. In the NLF region, the 6-month improvement response rate assessed by blinded investigators showed that Juvéderm? showed better outcomes than Restylane? ( RR=1.07, 95% CI: 0.89-1.32), while Belotero? was slightly inferior to Restylane? ( RR=0.97, 95% CI: 0.65-1.44), although the differences were not statistically significant. Subject-reported outcomes showed consistent trends with investigator assessments. For 6-month GAIS improvement, Juvéderm? and Restylane? showed comparable result within the HA filler category ( RR=1.01, 95% CI: 0.71-1.43). The collagen stimulator Ellansé? demonstrated numerically higher values than HA fillers ( RR=1.32, 95% CI: 0.86-2.08). However, none of these differences reached statistical significance. In midface treatments, Juvéderm? had more long-term evidence, with follow-up periods extending up to 24 months. Four studies reported numerically greater volume enhancement with Juvéderm? compared to Restylane?. For other facial areas, Juvéderm? had the most comprehensive clinical evidence, covering the widest range of injection sites. No relevant RCTs were available for collagen stimulators in these regions. Regarding patient satisfaction, 19 studies reported patient-reported outcomes, with Juvéderm? contributing 16 of them, and showing higher satisfaction in 6 head-to-head comparisons with Restylane?. In contrast, collagen stimulators currently lack such evidence. Safety result indicated that HA fillers were generally safe and well tolerated, while safety data for collagen stimulators remain limited due to insufficient high-quality evidence. Conclusion:Among the HA fillers, Juvéderm? has a large quantity and highest quality of clinical studies, and NMA result shows its superior efficacy in NLF. In comparison, the current evidence is still not sufficient to draw a clear conclusion for the PCL/PLLA due to a lack of adequate high-quality clinical evidence regarding its clinical efficacy, PROs, and safety.

Objective To establish a high-performance liquid chromatography method to detect empagliflozin and related substances in empagliflozin bulk drug and tablets,and to provide technical support for quality control and unified monitoring of empagliflozin bulk drug and its tablets.Methods A liquid chromatography development system with the full factorial design of experiments and the Box-Behnken model was used to screen and optimize the chromatographic parameters.Related substances were detected in empagliflozin API and empagliflozin tablets from different companies with the optimized chromatographic parameters.Results The optimized chromatographic parameters were obtained:Shim-pack GIST C18-AQ column(250 mm×4.6 mm,5 μm)was used,column temperature was 15 ℃,gradient elution with water-acetonitrile as mobile phase was as below,flow rate was 1.2 mL·min-1,detection wavelength was set at 224 nm.The specificity of the method is good,with recoveries ranging from 94.8％to 101.7％,and RSD ranging from 0.5％to 3.1％.The known single impurity in APIs and tablets is less than 0.05％,any other unknown single impurity is less than 0.06％,and the total amount of impurities are less than 0.3％.The related substances of supervised sampling are under good control.Conclusion The method is reliable and robust for determining related substances of empagliflozin and its tablets.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective To establish a high-performance liquid chromatography method to detect empagliflozin and related substances in empagliflozin bulk drug and tablets,and to provide technical support for quality control and unified monitoring of empagliflozin bulk drug and its tablets.Methods A liquid chromatography development system with the full factorial design of experiments and the Box-Behnken model was used to screen and optimize the chromatographic parameters.Related substances were detected in empagliflozin API and empagliflozin tablets from different companies with the optimized chromatographic parameters.Results The optimized chromatographic parameters were obtained:Shim-pack GIST C18-AQ column(250 mm×4.6 mm,5 μm)was used,column temperature was 15 ℃,gradient elution with water-acetonitrile as mobile phase was as below,flow rate was 1.2 mL·min-1,detection wavelength was set at 224 nm.The specificity of the method is good,with recoveries ranging from 94.8％to 101.7％,and RSD ranging from 0.5％to 3.1％.The known single impurity in APIs and tablets is less than 0.05％,any other unknown single impurity is less than 0.06％,and the total amount of impurities are less than 0.3％.The related substances of supervised sampling are under good control.Conclusion The method is reliable and robust for determining related substances of empagliflozin and its tablets.

Objective To investigate the therapeutic effects of copper-doped barium titanate(BaCuTiO4)piezoelectric materials combined with low-intensity pulsed ultrasound(LIPUS)to activate their piezoelectric-catalytic synergistic effect for treating implant-associated infections.Methods BaCuTiO4 coatings were synthesized on the surface of Ti-6Al-4V substrates using a hydrothermal method,and their surface morphology was characterized by scanning electron microscopy.The piezoelectric characteristics of the coatings were analyzed using a piezoresponse force microscope.An in vitro biofilm model of methicillin-resistant staphylococcus aureus(MRSA)was used,with barium titanate(BaTiO3)coatings serving as the control group.Under LIPUS intervention(1.0 W/cm2,1 MHz,10 min),the bacterial viability was assessed using colony counting to evaluate the antibacterial performance of the BaCuTiO4 coatings.Confocal microscopy was used to observe biofilm viability in different groups,assessing the biofilm removal capability of the coatings.Reactive oxygen species(ROS)generation in each group was detected using Rhodamine b as a probe to evaluate the catalytic efficiency of the coatings in generating ROS.Results Copper doping significantly reduced the piezoelectric coefficient of the coating(from 17.7 pm/V to 7.8 pm/V),bringing its piezoelectric performance closer to the requirements of natural bone tissues.Under LIPUS activation,the BaCuTiO4 coatings increased the generation efficiency of reactive oxygen species by 67.5％and effectively disrupted and removed biofilms formed by MRSA,achieving an antibacterial rate of 90.5％.Conclusions The BaCuTiO4 coatings achieve efficient antibacterial and biofilm-clearing functions through a piezoelectric-catalytic synergistic mechanism.Their piezoelectric properties are well-matched with natural bone tissues,promoting implant osseointegration.

ObjectiveTo observe the effect of Shenshu Fujian decoction on platelet-derived growth factor （PDGF）/naked cuticle homolog 2 （NKD2） /Wnt signaling pathway in rats with chronic renal failure （CRF）. MethodsSixty male SD rats were randomly divided into normal group， model group， Niaoduqing group （5 g·kg^-1）， low-dose Shenshu Fujian decoction group （5.5 g·kg^-1）， medium-dose Shenshu Fujian decoction group （11 g·kg^-1）， and high-dose Shenshu Fujian decoction group （22 g·kg^-1）， with 10 rats in each group. A CRF rat model was established by feeding a 0.5% adenine diet for 21 days. After successful modeling， intragastric administration was given once daily for 28 consecutive days. After treatment， the renal morphology of rats was observed. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Hematoxylin-eosin （HE） staining and Masson staining were used to detect renal histopathological changes， and collagen volume fraction （CVF） was calculated. Serum levels of inflammatory markers interleukin （IL）-1β and IL-6 were measured using enzyme-linked immunosorbent assay （ELISA）. The expressions of fibronectin 1 （FN1）， type Ⅰ collagen （ColⅠ）， α-smooth muscle actin （α-SMA）， platelet-derived growth factor receptor-β （PDGFR-β）， NKD2， dishevelled protein 2 （DVL2） and β-catenin in renal tissue were detected by immunohistochemistry and Western blot. ResultsCompared with the normal group， the model group showed significant renal pathological changes， a markedly increased kidney weight/body weight ratio （P<0.01）， significantly elevated CVF （P<0.01）， and notably increased serum levels of SCr， BUN， IL-1β， and IL-6 （P<0.01）. Expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were also significantly increased （P<0.01）. Compared with the model group， all treatment groups showed significantly decreased kidney weight/body weight ratios and CVF （P<0.01）， as well as markedly decreased serum SCr， BUN， IL-1β， and IL-6 levels. Protein expression levels of FN1， ColⅠ， α-SMA， PDGFR-β， NKD2， DVL2， and β-catenin in renal tissue were decreased， with more pronounced effects observed in the Niaoduqing， medium-dose， and high-dose Shenshu Fujian decoction groups （P<0.05， P<0.01）. ConclusionShenshu Fujian decoction improves renal function， reduces inflammation， and reverses renal fibrosis in CRF rats， possibly by downregulating the expression of PDGF/NKD2/Wnt signaling pathway-related proteins.