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.

Objective:To evaluate the feasibility and outcomes of transnasal endoscopic clipping of the paraclival internal carotid artery (ICA) in skull base surgery.Methods:The paraclival ICA was anatomically dissected in cadaveric head specimens. The clinical data of 15 patients with skull base lesions involving the ICA who admitted to the Department of Otorhinolaryngology Head and Neck Surgery at Tianjin Huanhu Hospital from January 2021 to December 2023 were retrospectively analyzed. Among them, 4 patients underwent transnasal endoscopic clipping of the paraclival ICA and concurrent lesion resection. The surgical methods were summarized, and the key points and indications of this technique were analyzed.Results:Intraoperative clipping of the ICA was successful and hemostatic in all 4 patients. Postoperatively, 3 patients had no complications, while 1 patient developed delayed ischemic cerebral infarction. Two patients were cured, 1 patient was maintained on immunotherapy, and 1 patient died. During follow-up, the clip was in situ in 1 patient, had detached in another, and was obscured by temporal muscle coverage in the remaining 2 patients.Conclusions:Transnasal endoscopic clipping of the paraclival ICA represents a potential option for managing the ICA in skull base surgery. However, it carries significant risks and limitations, mandating careful patient selection based on specific circumstances.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

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.

Objective:To observe and assess the clinical value of electrophysiology of ocular surface in the diagnosis and treatment of blepharospasm in Meige syndrome (MS).Methods:A single-center, cross-sectional study. A total of 413 patients diagnosed with MS and undergoing surgical treatment at the Henan Provincial Meige Syndrome Diagnosis and Treatment Center of the Henan Provincial Third People′s Hospital from May 2022 to December 2023 were included as the MS group. A total of 110 age- and gender-matched spouses of patients and community volunteers were selected as the control group. The bioelectricity detection program of the electrooculogram was used; the frequency bandwidth was set at 0.3 to 300.0 Hz. Surface electrodes were employed to record the surface electrophysiological manifestations of the corrugator supercilii muscle and the lower orbicularis oculi muscle, as well as the conditions and temporal characteristics of spasm waves. Based on the amplitude and waveform of the electrophysiology of ocular surface signals, it can be classified into 0-4 grades. The blepharospasm was divided into conditionally induced type, spastic type, reverse spastic type, and oro-ocular elicited type. All patients were treated with neural circuit occlusion, and the postoperative follow-up time was 4.1 (0.5-19.0) months. The distribution of different grades of electrophysiology of ocular surface in the MS and control group at baseline were observed, as well as within the MS group at the last follow-up visit. Additionally, the blepharospasm grades in the MS group were also assessed. The comparison of the distribution of the number of eyes with different grades of electrophysiology of ocular surface between groups was conducted using the Mann-Whitney U test. Results:At baseline, in the MS group, the number of cases with corrugator supercilii muscle amplitudes and morphologies graded from 0 to 4 were as follows: 15 (3.60%, 15/413) for grade 0, 95 (23.00%, 95/413) for grade 1, 142 (34.38%, 142/413) for grade 2, 127 (30.75%, 127/413) for grade 3, and 34 (8.24%, 34/413) for grade 4. In the control group, the corresponding numbers of individuals were 82 (74.54%, 82/110) for grade 0, 24 (21.82%, 24/110) for grade 1, 4 (3.64%, 4/110) for grade 2, 0 (0.00%, 0/110) for grade 3, and 0 (0.00%, 0/110) for grade 4. For the orbicularis oculi muscle, there were 35 cases (8.47%) in grade 0, 124 cases (30.03%) in grade 1, 150 cases (36.32%) in grade 2, 90 cases (21.79%) in grade 3, and 14 cases (3.39%) in grade 4 in the MS group. In the control group, there were 86 cases (78.18%) in grade 0, 24 cases (21.82%) in grade 1, and 0 cases in grades 2, 3, and 4. There were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between the MS and control group ( Z=-14.51, -13.86; P<0.001). Meanwhile, there were statistically significant differences in the distribution of the number of eyes with different electrophysiology of ocular surface grading of the corrugator supercilii muscle and the orbicularis oculi muscle between preoperation and at the last follow-up in the MS group ( Z=-16.52, -17.36; P<0.001). In the MS group, there were 61 (14.77%, 61/413), 306 (74.09%, 306/413), 27 (6.54%, 27/413) and 19 (4.60%, 19/413) cases of blepharospasm conditionally induced type, spasm type, reverse spasm type and oro-ocular elicited type, respectively. Conclusion:The electrophysiology of the ocular surface can objectively reflect the activity of periocular neuromuscular.

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.

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.