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.

Colorectal cancer （CRC）， as a highly prevalent malignant tumor worldwide， continues to rank among the leading malignancies in both incidence and mortality. At present， the clinical treatment of CRC mainly relies on surgery， radiotherapy， chemotherapy， and drug therapy. However， due to individual differences among patients and the emergence of drug resistance in cancer cells， the postoperative recurrence rate remains high， significantly affecting patient prognosis. In recent years， traditional Chinese medicine （TCM） has attracted extensive attention in the field of tumor prevention and treatment because of its therapeutic advantages of multi-component， multi-target， multi-pathway， and holistic regulation. Aberrant activation of the Hedgehog signaling pathway is closely associated with the occurrence of various cancers. Studies have shown that the Hedgehog signaling pathway plays a key regulatory role in the occurrence and development of CRC. This pathway regulates the expression of downstream target genes through glioma-associated oncogene homolog （GLI） transcription factors and participates in biological processes such as tumor cell proliferation， apoptosis， invasion， and metastasis. It exerts anti- CRC effects through mechanisms including inducing apoptosis of CRC cells， inhibiting cancer cell proliferation， reversing drug resistance， and suppressing epithelial-mesenchymal transition （EMT）， thereby influencing the progression of CRC. This article systematically reviews the latest research progress in China and abroad and comprehensively discusses the molecular regulatory mechanisms of the Hedgehog signaling pathway in CRC. It particularly focuses on the specific mechanisms by which active components of Chinese medicine， such as alkaloids and terpenoids， and Chinese medicine compound formulas， such as Baitouwengtang and Zhizhenfang， exert anti-CRC effects by interfering with the Hedgehog-GLI signaling axis. By integrating and analyzing the molecular relationship between the Hedgehog signaling pathway and the pathological progression of CRC， and combining the TCM theories of "holistic concept" and "syndrome differentiation and treatment"， this article explores new TCM therapeutic strategies based on the Hedgehog signaling pathway， with the aim of providing innovative theoretical foundations and practical guidance for the prevention and treatment of CRC with TCM.

OBJECTIVE To evaluate the status of microbial contamination in the environment of respiratory tract specimens sampling rooms and observe the association of the factors such as design and layouts of the sampling rooms with the potential risk of infections in the environment so as to provide scientific bases for optimizing the construction standards of fever clinics of the medical institutions.METHODS The sampling rooms of fever clinic were chosen from 10 tertiary or above medical institutions of Hangzhou,and the samples were collected from the key sites such as air,object surfaces and hands of health care workers.The respiratory tract pathogens in the sam-ples were detected by FilmArray full-automatic medical PCR analysis system,and the pathogens in the samples were detected by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry(MALDI-TOF MS).The data including the areas,windows,mechanical ventilation facilities,physical partitions,frequencies and modes of disinfection and daily amounts of diagnosis and treatment of the 10 sampling rooms were investigated,and the univariate analysis was performed for their association with the microbial contamination of environment.RESULTS The isolation rate of respiratory tract pathogens was 10.00％(4/40),respiratory syn-cytial virus,human rhinovirus and adenovirus were dominant among the respiratory tract pathogens.The isolation rate of bacteria was 71.88％(23/32),Staphylococcus ho minis and Staphylococcus epidermidis were the major species of opportunistic pathogens isolated.The result of univariate analysis indicated that both the presence of windows(P=0.012)and mechanical ventilation facilities(P=0.047)were associated with the potential risk of infections in the environment(P＜0.05);while the factors such as the areas of sampling rooms,physical parti-tions,disinfection modes and daily amounts of diagnosis and treatment were not remarkably associated with the potential risk of infections in the environment.CONCLUSION It is an effective way to physically separate the air-flow from other areas or fix the mechanical ventilation facilities to create proper airflow during the construction of fever clinic sampling rooms so as to reduce the potential risk of infections in the environment of sampling rooms.

AIM To investigate the differences between boiled powder and decoction of Ermiao Powder.METHODS GC-MS was used to identify volatile constituents,after which the content determination of linalool,4-terpineol,α-terpineol,β-eucalyptol and taxifolin in distillate was performed,evaporation rate curve was drawn.The rat model for collagen-induced arthritis was established,then HE and SO/FG staining were conducted,and body weight,footpad swelling degree,arthritis score,immune organ(spleen,thymus)indices,serum inflammatory factors(IL-10,IL-6),ankle joint structure(foot claw swelling,micro-CT)and locomotor ability were detected.RESULTS Total 43 and 26 volatile constituents were identified in boiled powder and decoction,respectively.With the extension of boiling time,the average evaporation rates of 5 volatile constituents in the boiled powder distillate demonstrated the trends of first increase and then decrease,which reached a maximum at 15-20 min;those in the decoction distillate displayed the trends of decrease,which were not detected after 15 min except for β-eucalyptol.Compared with the decoction,the boiled powder exhibited stronger effects on improving foot swelling and arthritis score,alleviating pathological changes in joint tissues,inhibiting inflammatory factors and restoring motor ability.CONCLUSION More volatile constituents are observable in the boiled powder of Ermiao Powder than those in its decoction,along with stronger anti-rheumatoid arthritis activity.The optimal decocting endpoint is determined to be within 15 min in boiling water.

Based on the target recognition ability of split aptamer and intelligent analytical capability of molecular logic gate,in this work,two split aptamers were integrated into"AND"logic gate to construct a novel ortho-nucleic acid fluorescence sensor for simultaneous detection of thrombin and myoglobin.When there was one target,the response of the signal was only a single fluorescence output signal,which was used as an evaluation standard for early low-risk judgment.When two targets coexisted,the split aptamer bound to the target to form a ternary complex and led to the head and tail ortho-nucleic acid effect respectively,and triggered the G4 chain to enhance the fluorescence signal of thioflavin T and the fluorescence signal quenching of Cyanine 3,which could be used as an evaluation criterion for early high-risk judgement.Under the optimal conditions,the linear range for detection of thrombin was 3-200 nmol/L,with a correlation coefficient of 0.9931 and a detection limit of 0.97 nmol/L,and the linear range for detection of myoglobin was 6-400 nmol/L,with a correlation coefficient of 0.9933,and a detection limit of 2.14 nmol/L.The method was applied to simultaneous determination of thrombin and myoglobin in clinical serum samples,and the recoveries were 85.4%-118.3%and 85.8%-119.9%,respectively,with relative standard deviations of less than 6.5%.Compared with the standard method,the relative error range was from-8.8%to 5.6%.In addition,the logical diagnosis results of 4 serum samples were high-risk of acute myocardial infarction in 2 cases and low-risk in 2 cases.The ″AND″ logic gate ortho-nucleic acid fluorescence sensing method showed many advantages such as high selectivity,rapidity,accuracy and simultaneous detection,which offered important reference for early diagnosis of acute myocardial infarction,and also provided a general detection design strategy and platform for simultaneous detection of biomarkers.

Objectives:Comparative analysis of the beagles acute-phase electrocardiographic,hemodynamic,left ventricular flow field status,and energy consumption characteristics of pacing at different sites of conduction system may help to elucidate the scientific mechanism of left bundle branch pacing(LBBP)as a option of physiological pacing therapy.Methods:Eight healthy adult beagles were used in this study.Initially,an active fixation lead was implanted in the right atrial appendage,followed by implantation of another active fixation lead at the right ventricular apex,distal His bundle,and left bundle septal branch,respectively.After connecting a dual-chamber pacemaker,electrocardiographic and acute phase hemodynamic parameters under sinus rhythm,right ventricular apex pacing(RVAP),distal His bundle pacing(DHBP),and LBBP states were collected and analyzed.Three complete cardiac cycles of standard apical three-chamber color Doppler dynamic images were acquired under vector flow mapping(VFM)mode.Offline analysis was performed on obtained parameters including isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,atrial contraction period,and left ventricular intracavitary energy consumption.These parameters were compared under pacing at different sites and the linear correlations of major parameters were analyzed.Results:The QRS duration of baseline intrinsic sinus rhythm,RVAP,DHBP and LBBP were(45.0±4.0)ms,(98.4±6.2)ms,(50.0±4.5)ms and(62.0±4.7)ms,respectively.The LBBP-QRS duration was significantly wider than intrinsic sinus rhythm and DHBP,but significantly narrower than RVAP(all P<0.01).Compared with baseline AOO mode(the pacing rate was performed at 10 beats/min above the intrinsic heart rate),the change of acute phase maximum left ventricular pressure rise rate(LVdP/dtmax)in RVAP,DHBP and LBBP was([-7.89±5.67]% ),([0.74±2.05]% )and([-0.14±3.59]% ),respectively.There was no significant difference in LVdP/dtmax changes between DHBP and LBBP(P=0.667),but both pacing modalities were significantly better than RVAP(all P<0.01).The average energy consumption of the left ventricle under RVAP was significantly higher than that of intrinsic sinus rhythm,DHBP,and LBBP in isovolumic contraction period,rapid ejection period,isovolumic relaxation period,rapid filling period,and atrial contraction period(all P<0.01).However,there was no statistically significant difference in energy consumption among intrinsic sinus rhythm,DHBP,and LBBP during the above five phases(all P>0.05).DHBP and LBBP did not show a significant increase in the number of left ventricular vortices,vortex area,and circulation intensity compared to intrinsic sinus rhythm,and LBBP did not show a significant increase in vortex area and circulation intensity compared to DHBP.Conclusions:Although LBBP canines significantly prolonged the paced QRS duration,it showed no significant differences in acute phase left ventricular hemodynamics,left ventricular flow field status,and energy consumption compared to intrinsic sinus rhythm and DHBP.Performance of LBBP was superior to RVAP.This study may contribute to revealing the theoretical basis of LBBP as a feasible physiological pacing therapy.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*