Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） acetic acid（D1）and 4-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） butanoic acid （D2）. Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro （P<0.01）. However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

ObjectiveTo evaluate the effect of action observation therapy (AOT) combined with low-frequency repetitive transcranial magnetic stimulation (rTMS) on post-stroke unilateral spatial neglect. MethodsA total of 108 patients with post-stroke unilateral spatial neglect admitted to Suqian Integrated Traditional Chinese and Western Medicine Hospital from January, 2023 to March, 2024 were enrolled. The patients were randomly allocated to AOT group, rTMS group and combined group with 36 patients in each group. All the groups received conventional treatment. The AOT group additionally received AOT, the rTMS group additionally received rTMS, and the combined group received both AOT and rTMS, for four weeks. Before and after treatment, the patients were assessed using the Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment (FMA), modified Barthel Index (MBI), Chinese Behavioural Inattention Test-conventional test (CBIT-C) and CBIT-behavioural test (CBIT-B). The latency and amplitude of the N20 potential on the affected side were also measured. ResultsThree patients dropped out from each group. After intervention, significant main effects of time (F > 77.096, P < 0.001) and group (F > 5.119, P < 0.01) and significant time-by-group interaction effects (F > 3.320, P < 0.05)were observed in the MoCA, FMA, MBI, and CBIT-C scores. For the CBIT-B score, the main effects of time (F = 367.430, P < 0.001) and group (F = 4.995, P = 0.008) were significant. After intervention, MoCA, FMA, MBI, CBIT-C and CBIT-B scores, and N20 amplitude and latency were better in the combined group than in the AOT and rTMS groups (P < 0.05). ConclusionThe combination of AOT and rTMS may further ameliorate cognitive function, motor function, activities of daily living, and the degree of spatial neglect in post-stroke patients with unilateral spatial neglect, potentially attributable to improved nerve conduction function.

An analysis of 24 144 norovirus sequences from Asia and Russia deposited in GenBank between 1995 and 2023 was conducted,to understand the temporal and spatial variations in norovirus genotypes in these regions.Norovirus sequences from Asia and Russia were downloaded in FASTA format from GenBank for the years 1995-2023,and analyzed in Excel,R language,and GraphPad Prism for data visualization.The number of norovirus sequences submitted to GenBank increased annually from 2004 and peaked in 2015.Notably,China and Japan contributed 62.3％of all submitted norovirus sequences.These sequences encompassed 31 capsid genotypes(C-type),with GⅠ accounting for 9％and GⅡ accounting for 90％.Additionally,49 polymerase types(P-type)were identified,along with 68 combinations of CP types;among the analyzed recombinant sequences(4 460 entries in total),approxi-mately 41％belonged to three predominant recombinant strains:GⅡ.2[P16],GⅡ.4[P31],and GⅡ.4[P16].This analysis provides valuable insights into the distribution characteristics of norovirus genotypes across Asia and Russia over time,thereby supporting vac-cine design and evaluation efforts.

AIM To establish an HPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,oxypaeoniflorin,catechin,epicatechin,albiflorin,paeoniflorin,rutin,calycosin-7-glucoside,syringaldehyde,ferulic acid,coumarin,ononin,calycosin,cinnamic alcohol,cinnamic acid,benzoylpaeoniflorin,cinnamaldehyde,astragaloside,astragaloside Ⅲ,6-gingerol in Huangqi Guizhi Wuwu Decoction.METHODS The analysis was performed on a 30 ℃ thermostatic Thermo Scientific Hypersil GOLD column(150 mmx4.6 mm,3 μm),with the mobile phase comprising of 0.015％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electrospray ionization source was adopted in positive and negative ion modes with multiple reaction monitoring.RESULTS Twenty-one constituents showed good linear relationships within their own ranges(r＞0.990 5),whose average recoveries were 93.99％-108.52％with the RSDs of 1.04％-5.97％.CONCLUSION This simple,feasible,stable and reliable method can be used for the quality control of Huangqi Guizhi Wuwu Decoction.

AIM To evaluate the quality consistency of Tongmai Granules,Tongmai Tablets,Tongmai Capsules and Tongmai Oral Liquid.METHODS The HPLC fingerprints were established,after which the contents of danshensu,protocatechuic aldehyde,3'-hydroxy puerarin,puerarin,puerarin apioside,daidzin,ferulic acid,salvianolic acid B and salvianolic acid A were determined,and cluster analysis and principal component analysis were adopted in the quality analysis from the perspective of daily intake.RESULTS There were 21 common peaks in the fingerprints for 39 batches of samples with the similarities of 0.765-0.997.Various batches of samples were clustered into 5 categories,2 principal components demonstrated the accumulative variance contribution rate of 83.53％ .The daily intakes of various constituents in different dosage forms exhibited obvious differences,especially for that of salvianolic acid B,which were low in tablets and capsules,and their heterogeneities existed among the same dosage forms.CONCLUSION This simple and accurate method can provide a reference for the quality evaluation of Tongmai preparations from different manufacturers.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

An analysis of 24 144 norovirus sequences from Asia and Russia deposited in GenBank between 1995 and 2023 was conducted,to understand the temporal and spatial variations in norovirus genotypes in these regions.Norovirus sequences from Asia and Russia were downloaded in FASTA format from GenBank for the years 1995-2023,and analyzed in Excel,R language,and GraphPad Prism for data visualization.The number of norovirus sequences submitted to GenBank increased annually from 2004 and peaked in 2015.Notably,China and Japan contributed 62.3％of all submitted norovirus sequences.These sequences encompassed 31 capsid genotypes(C-type),with GⅠ accounting for 9％and GⅡ accounting for 90％.Additionally,49 polymerase types(P-type)were identified,along with 68 combinations of CP types;among the analyzed recombinant sequences(4 460 entries in total),approxi-mately 41％belonged to three predominant recombinant strains:GⅡ.2[P16],GⅡ.4[P31],and GⅡ.4[P16].This analysis provides valuable insights into the distribution characteristics of norovirus genotypes across Asia and Russia over time,thereby supporting vac-cine design and evaluation efforts.