Objective: To determine the clinical efficacy of platelet-rich plasma (PRP) injection combined with warm acupuncture and moxibustion for treating patients with knee osteoarthritis and cold dampness obstruction syndrome. Methods: One hundred and twenty-eight patients with knee osteoarthritis and cold dampness obstruction syndrome who visited the Rehabilitation Department and Orthopedics Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine from January 2023 to March 2024 and who met the inclusion and exclusion criteria were randomly divided into an experimental (n=64) and control group (n=64) using the random number table method. The experimental group was treated with PRP injection combined with warm acupuncture and moxibustion, whereas the control group was treated with normal saline injection combined with warm acupuncture and moxibustion treatment. PRP and normal saline injections were administered once every two weeks, a total of four times. Patients were treated with warm acupuncture and moxibustion once a day, six times a week, for four consecutive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Traditional Chinese Medicine (TCM) syndrome, visual analog scale (VAS), and Lysholm scores were determined before treatment, at week 4 and week 8 of treatment, and week 16 of follow-up. Serum interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), bone gla protein(BGP), and cartilage oligomeric matrix protein (COMP) levels were compared between the two groups before and after 8 weeks of treatment. The clinical efficacy and safety indicators between the two groups were also compared. Results: There was no statistical difference in baseline data such as gender, age, disease duration, and body mass index between the two groups of patients. Compared with before treatment, both groups showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm scores at 4, 8, and 16 weeks after treatment. After treatment, serum IL-6, MMP-3, TNF-α, and COMP levels decreased, whereas serum OPG and BGP levels increased (P<0.05). Compared with the control group, patients in the experimental group showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm score at 4, 8, and 16 weeks after treatment. Compared with the control group, patients in the experimental group showed decreased serum IL-6, MMP-3, TNF-α, and COMP levels and an increase in serum OPG and BPG levels after treatment (P<0.05). The total effective rate of the experimental group was 91.94%, higher than that of the control group (81.97%; P<0.05). Conclusion PRP injection combined with warm acupuncture and moxibustion can improve various TCM symptoms, improve knee joint function and bone metabolism, and reduce inflammation in patients with knee osteoarthritis and cold dampness obstruction syndrome.

ObjectiveTo systematically evaluate the efficacy and safety of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines in the treatment of coronary microvascular disease （CMD）. MethodsPubMed， Cochrane Library， CNKI， Wanfang Data， and VIP were searched for the randomized controlled trials （RCTs） on the treatment of CMD with Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis with the time interval from inception to December 31， 2023. The primary outcome indicators included the index of microcirculatory resistance （IMR）， coronary flow reserve （CFR）， and corrected TIMI flow frame count （cTFC）. The secondary outcome indicators included symptomatic efficacy， left ventricular ejection fraction （LVEF）， hypersensitive C-reactive protein （hs-CRP）， nitric oxide （NO）， and adverse events. Cochrane risk-of-bias assessment tool 2.0 （RoB 2.0） and Stata 17.0 were used for literature quality evaluation and meta-analysis of the included RCTs. The Grading of Recommendations， Assessment， Development and Evaluation （GRADE） was used to evaluate the quality of evidence. ResultsA total of 36 RCTs were included in this study， involving 3 029 patients. Compared with conventional Western medicine alone， the combined use of Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis and Western medicine reduced the IMR ［mean difference （MD）=-5.93， 95% confidence interval （95%CI） ［-8.73，-3.14］， n=382， P<0.01］， cTFC （MD=-9.35， 95%CI ［-13.94，-4.76］， n=618， P<0.01）， and hs-CRP ［standard mean difference （SMD）=-1.50， 95%CI ［-1.90，-1.11］， n=1 483， P<0.01］， improved the CFR （SMD=1.14， 95%CI ［0.08，2.19］， n=304， P=0.03）， symptomatic efficacy ［relative risk （RR）=1.36， 95%CI ［1.21，1.53］， n=756， P<0.01］， LVEF （MD=4.39， 95%CI ［2.31，6.47］， n=533， P<0.01）， and NO （SMD=3.16， 95%CI ［2.07，4.25］， n=946， P<0.01） of CMD patients. In terms of safety， the combined therapy reduced the occurrence of adverse events in CMD patients （RR=0.49， 95%CI ［0.29，0.82］， n=591， P=0.01）. GRADE showed moderate quality evidence for adverse events， low quality evidence for cTFC， symptomatic efficacy， LVEF， and NO， and very low quality evidence for IMR， CFR， and hs-CRP. ConclusionBased on microcirculatory function indicators， the combined use of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines and Western medicine may further improve the coronary microvascular function in CMD patients with good safety. The above conclusions remain to be verified with high-quality clinical trials.

A rapid and accurate method for textile fiber identification was developed for quality control and consumer protection.This method utilized electric soldering iron burning-mesh collision enhanced microtube plasma ionization mass spectrometry(ESIB-MC-μTP-MS)to acquire textile fiber MS data and used a random forest(RF)prediction model to identify fiber composition based on these MS data.The MC-μTP device involved in the method was a homemade low-temperature plasma ionization device constructed using cost-effective and readily available components.The system was applicable for direct analysis of small amount of textile samples without any complex sample pretreatment processes.Characteristic thermal decomposition products of different fibers were generated via soldering iron burning(350℃)in ambient atmosphere,and were subsequently analyzed by a mass spectrometer,with each analysis completed within 5 s.Raw MS data underwent noise reduction,normalization,and global binning steps to form a dataset,and its intrinsic class separability was evaluated using principal component analysis(PCA)combined with k-means clustering.Then,the RF model was trained based on the dimensionality-reduced textile fiber dataset.After grid search optimization,this model demonstrated robust performance with a 0.9762 out-of-bag score,a 0.9683 cross-validation accuracy(5-fold),and a 0.9636 test accuracy,supported by precision,recall,and F1-scores exceeding 0.889 for all fiber classes.The method was applied to analysis of 30 luxury apparel samples from eight brands,among which 20 samples achieved 100%prediction confidence,aligning with labeled compositions.The identification result of two low-confidence samples was further confirmed using attenuated total reflection Fourier transform infrared spectroscopy(ATR-FT-IR).The method has been proven to be simple,portable and with minimal sample requirements for on-site customs inspections,providing a viable tool in the fight against counterfeit products,therefore supporting regulatory enforcement and consumer trust in the textile goods market.

Due to the poor ionization efficiency and the weak mass spectrometry(MS)intensity of weakly polar substances,direct analysis using the traditional electrospray ionization mass spectrometry(ESI-MS)is a big challenge.In this study,a novel rapid on-site detection method of four prohibited sex hormones in cosmetics was proposed using online derivatization strategy coupled with a miniature mass spectrometer.The target substances in the samples were extracted by a custom-made polyaniline/multi-walled carbon nanotube solid-phase microextraction(SPME)probe.The stirring speed was 200 r/min,the extraction temperature was 40℃,and the extraction time was 2 min.A pulled dual-channel θ borosilicate glass capillary emitter was used as the nano-ESI ion source.The SPME probe was inserted into the channel containing methanol in theθborosilicate glass capillary.When the spray voltage was applied,the four sex hormones were desorbed and formed spray microdroplets,which then collided with the hydroxylamine microdroplets generated from the other channel.The microdroplets of reaction product entered into the miniature mass spectrometer for direct analysis.The limits of detection(LOD)and limits of quantification(LOQ)for the four sex hormones were 10-20 ng/mL and 20-50 ng/mL,respectively.The recoveries were from 84.6%to 107.8%with the relative standard deviations(RSD)from 4.1%to 11.6%.Compared to detection without derivatization,the MS signals of the four target substances were increased by 3 to 15 times.This method was simple,rapid,highly efficient and sensitive,and suitable for on-site rapid analysis of weakly polar sex hormones in cosmetics.

As an adjuvant therapy,transarterial chemoembolization(TACE)can prolong the disease-free survival and overall survival of patients with primary liver cancer(PCL).However,postoperative adverse reactions and recurrence still possibly persist.Based on years of clinical practice,Professor Lin Lizhu proposes that patients with PCL undergoing TACE exhibit pathological mechanisms characterized by deficiency,stagnation,toxicity,and stasis.In clinical practice,these patients can be treated with Chinese herbal medicine based on the therapeutic principle of strengthening spleen and soothing liver.The treatment strategy involves:invigorating spleen and stomach to restore healthy qi,soothing liver and nourishing blood to support liver function,and detoxifying and dispersing stasis to prevent recurrence.Derived from the classic formula Sini San,Professor Lin has developed Sini Kang'ai Formula,which mainly consists of Eupolyphaga Steleophaga,Bupleuri Radix,Paeoniae Radix Alba,Aurantii Fructus Immaturus,Glycyrrhizae Radix et Rhizoma,Codonopsis Radix,Persicae Semen,Cremastrae Pseudobulbus Pleiones Pseudobulbus,etc.In clinical application,Sini Kang'ai Formula should be flexibly modified depending on the characteristic symptom patterns of patients during the perioperative period of TACE,thus to alleviate postoperative adverse reactions,prevent tumor recurrence,prolong disease-free survival and overall survival,and improve patients' quality of life.

Obstructive sleep apnea (OSA) is a global public health concern characterized by repeated upper airway collapse during sleep. Research indicates that OSA is a risk factor for the development of various diseases, including cardiovascular disease, metabolic disorders, respiratory diseases, neurodegenerative diseases, and cancer. Exosomes, extracellular vesicles released by most cell types, play a key role in intercellular communication by transporting their contents-such as microRNA, messenger RNA, DNA, proteins, and lipids-to target cells. Intermittent hypoxia associated with OSA alters circulating exosomes and promotes a range of cellular structural and functional disturbances involved in the pathogenesis of OSA-related diseases. This review discusses the potential roles of exosomes and exosome-derived molecules in the onset and progression of OSA-associated diseases, explores the possible underlying mechanisms, and highlights novel strategies for developing exosome-based therapies for these conditions.
Humans ; Exosomes/physiology* ; Sleep Apnea, Obstructive/metabolism* ; Animals ; MicroRNAs/metabolism*

The chemical constituents of sesquiterpenes from 95% ethanol extract of Aquilariae Lignum Resinatum were isolated and purified by various column chromatography techniques, including silica gel, Sephadex LH-20, octadecylsilyl(ODS), and semi-preparative high performance liquid chromatography(HPLC). Their planar structures and absolute configurations were elucidated by ultraviolet(UV) spectrometry, infrared(IR) spectroscopy, mass spectrometry(MS), nuclear magnetic resonance(NMR), electronic circular dichroism(ECD), and other techniques. Eight sesquiterpenoids were isolated and identified as(+)-(7R,10R)-selina-4,11-dien-12-dimethoxy-15-al(1),(+)-(7R,10R)-selina-4,11-diene-12,15-dial(2), agalleudesmanol B(3), aquisinenoid C(4), 12,15-dioxo-α-selinen(5), agarospiranic aldehyde B(6), neopetasane(7), and eremophila-7(11),9-dien-8-one(8). Compound 1 was a new compound, and it was the first time to find a dimethoxy substitution on the side chain of eudesmane-type sesquiterpene skeleton.
Sesquiterpenes/isolation & purification* ; Thymelaeaceae/chemistry* ; Molecular Structure ; Drugs, Chinese Herbal/isolation & purification* ; Magnetic Resonance Spectroscopy

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective To investigate the role of peptidyl prolyl cis-trans isomerase 1(Pin1)in mediating stemness of tumor cells and the molecular mechanism of inducing epithelial-mesenchymal transition(EMT)in cervical cancer cells.Methods The Siha and Hele cells of Pin1 low-expression stable transfection uterine cervical neoplasm cell lines were constructed using lentivirus transfection technology and were divided into control group(shPin1-NON),knockdown group 1(shPin1-1)and knockdown group 2(shPin1-2).Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)were used to detect the expressions of Sex-determining region Y transcription factor 2(SOX2),Aldehyde dehydrogenase 1A1(ALDH1A1),and Cell adhesion molecule 44(CD44).The serum-free spheroidization method was used to induce cervical cancer spheroids,with the adherent culture of cervical cancer cells as a control.Subsequently,Western blotting and qRT-PCR were employed to detect the expression of SOX2,ALDH1A1 and CD44 in both spheroid cells and adherent cells.Spheroid formation assay was used to detect the spheroid formation of cervical cancer cells after Pin1 knockdown.Transwell assay was used to detect the migration and invasion abilities of cervical cancer cells following down-regulation of Pin1.Western blotting and qRT-PCR were used to detect the expression of E-cadherin and N-cadherin attribute proteins in cervical cancer cells after transfection with pin1 low expression lentivirus.Western blotting and qRT-PCR were also used to assess the effects of Pin1 low expression on the expression levels of key proteins(c-Jun and c-Fos)of the transcriptional complex of Activator protein 1(AP-1).Immunofluorescence combined with co-immunoprecipitation assays were conducted to detect the interaction and colocalization of Pin1 with c-Jun.Results In Siha and Hele cells,the mRNA and protein expression levels of Pin1,SOX2,ALDH1A1 and CD44 in shPin1-NON group were significantly higher than those in shPin1-1 group and shPin1-2 group(P<0.05).The expression levels of SOX2,ALDH1A1 and CD44 mRNA and protein in cervical cancer spheroid group were significantly higher than those in adherent cervical cancer cells(P<0.05).Compared with shPin1-NON group,the spheroidism and migration invasion abilities of shPin1-1 group and shPin1-2 group were significantly reduced(P<0.05).Compared with shPin1-NON group,the mRNA and protein expressions of E-cadherin in shPin1-1 and shPin1-2 groups were significantly increased(P<0.05),while the mRNA and protein expression levels of N-cadherin were significantly decreased(P<0.05).The mRNA and protein expression levels of c-Jun and c-Fos in shPin1-NON group were significantly higher than those in shPin1-1 group and shPin1-2 group(P<0.05).Conclusions Down-regulation of Pin1 can inhibit the stemness and migration invasion of cervical cancer cells,and Pin1 may mediate AP-1 to regulate the occurrence of stemness-induced epithelial-mesenchymal transition in cervical cancer cells.

Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.