Objective To mine the risk signals of adverse drug events(ADEs)related to lecanemab through the U.S.Food and Drug Adminstration Adverse Event Reporting System(FAERS)database,to provide a reference for the safe clinical use of lecanemab.Methods Data on adverse events related to lecanemab from the fourth quarter,2010 to the second quarter 2024 in the FAERS were collected.Potential ADE signals were mined using the reporting odds ratio(ROR)method,Medicines and Healthcare Products Regulatory Agency(MHRA)method,Bayesian confidence propagation neural network(BCPNN)method and multi-item gamma Poisson shrinker(MGPS)method.The top 30 ADEs in terms of report frequency and signal strength,as well as ADEs categorized by system organ class(SOC),were statistically analyzed.Results A total of 868 adverse event reports related to lecanemab were collected,involving 1,986 instances of ADEs with 38 related ADE identified,the proportion of serious ADEs was 23.39％,and 87.15％of ADEs occurred in the first 3 months after the initiation of the drug.The top 30 PT signals in reported cases were headache,chills,fatigue,effusion type amyloid-related imaging abnormalities(ARIA-E),hemorrhage-type amyloid-related imaging abnormalities(ARIA-H),and so on.The top 30 signals in terms of signal intensity mainly included ARIA-E,ARIA-H,brain fog,infusion-related reactions.ADEs related to nervous system diseases were the most common.Fifteen new suspected or serious ADEs not recorded in the instructions were discovered,such as brain fog,formication,status epilepticus.Conclusion Risk assessment of patients'medication should be conducted before clinical use of lecanemab,especially in the first 3 months of the medication period,focus should be placed on monitoring common ADEs,such as ARIA-E,ARIA-H,infusion-related reactions.Attention also needs to be paid to the newly discovered suspected ADEs,to ensure the patients'medication safety.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

AIM To investigate the protective effect of Sanfeng Tongqiao Dropping Pills against house dust mite(HDM)-induced allergic asthma in mice.METHODS Compared to the intact BALB/c mice in the blank control group,the BALB/c mice randomly assigned into the model group,the dexamethasone group(0.67 mg/kg),and the low-dose,medium-dose,and high-dose Sanfeng Tongqiao Dropping Pills groups(15,30 and 60 mg/kg),were induced into acute allergic asthma models via weekly intraperitoneal sensitization with 0.1 mL HDM solution(0.5 mg/mL)for three weeks followed by three consecutive daily intranasal challenges with 10 μL HDM solution(2.5 mg/mL)starting in the third week.The drug administered continuously 7 days after the last excitation.The mice had their airway reactive Penh value detected,their pulmonary pathological changes observed by HE staining,their blood eosinophils(EOS)counted,their Th2 cytokines in lung tissue and serum IgE levels detected by ELISA,and their number of peripheral blood mononuclear cells(PBMC)and pulmonary Th2 cells detected by flow cytometry.Chronic allergic asthma was induced in grouped BALB/c mice through repeated intranasal challenges with 10 μL HDM solution(2.5 mg/mL)administered five times weekly for five consecutive weeks.Drug treatment continued for 14 days following the final challenge.After the final treatment,the mice had their pulmonary pathological changes observed by HE staining,and their levels of Th2 cytokines in B ALF and lung tissue and serum IgE detected by ELISA.RESULTS Compared to the blank control group,the acute allergic asthma model group exhibited increases in Penh value,EOS count and IgE level in serum,IL-4 and IL-5 levels in lung tissue(P＜0.01);obvious pulmonary inflammatory cells infiltration,and thickened airway wall;and increase in pulmonary number of Th2 cells(P＜0.01).Compared to the model group,the groups intervened with Sanfeng Tongqiao Dropping Pills demonstrated decreased Penh value,serum EOS count,IgE level and IL-5 level in lung tissue(P＜0.05,P＜0.01);reduced pulmonary inflammatory infiltration and alleviated airway wall thickening;and decreased number of pulmonary Th2 cells.Compared to the blank group,the chronic allergic asthma model group showed obvious pulmonary inflammatory infiltration and airway wall thickening;and increased EOS count and IgE level in serum,IL-4 and IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).Compared to the model group,the groups intervened with either medium-dose or high-dose Sanfeng Tongqiao Dropping Pills demonstrated reduced pulmonary inflammatory infiltration;and decreased serum EOS count,IgE level,IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).CONCLUSION Sanfeng Tongqiao Dropping Pills reduce Th2 cells in peripheral blood and lung tissue,suppress type 2 inflammation,and thereby alleviate allergic asthma.

ObjectiveTo investigate the contamination status, transmission risk and drug resistance of Klebsiella pneumoniae (KP) on the object surfaces in the surrounding environment of hospitalized patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) , so as to provide a scientific guidance for the prevention and control of healthcare-associated infection. MethodsSamples from the surfaces of objects in the surrounding environment of CRKP infected patients living in the intensive care unit (ICU) and hand specimens from healthcare workers were collected for KP isolation and identification, as well as drug susceptible test in a medical institution located in Minhang District, Shanghai from 2021 to 2023. Additionally, both univariate and multivariate logistic regression analyses were used to identify the influencing factors associated with KP contamination in the hospital environment. ResultsA total of 546 surface samples were collected from the surrounding environment objects of 15 patients infected with CRKP, with a KP detection rate of 6.59% (36/546).The KP detection rate in the ICU of general ward (10.22%) was higher than that in the ICU of emergency department (2.94%) (χ²=12.142, P<0.001). Moreover, the KP detection rate on the surfaces of patient-contacted items (15.66%) was higher than that on shared-use items (6.25%), cleaning items (10.00%), and medical supplies (3.30%) (χ²=17.943, P<0.001). Besides, the detection rate of KP in items sent out of hospital for disinfection (15.38%) was higher than that in those self-disinfected (4.20%) (χ²=19.996, P<0.001).The highest detection rate of KP was observed in high-temperature washing (15.13%, 18/119) (χ²=21.219, P<0.001), while the lowest detection rate was observed in antibacterial hand sanitizer with trichlorohydroxydiphenyl ether sanitizing factor (0, 0/60) ( χ²=21.219, P<0.001).The detection rate of KP in samples taken more than 24 hours after the last disinfection (23.08%) was higher than that in those taken at 4 to24 hours (12.90%) and less than 4 hours (4.22%) (χ²=23.398,P<0.001).ICU of general ward (OR=4.045, 95%CI: 2.206‒7.416), patient-contacted items (OR=3.113, 95%CI: 1.191‒8.141), and self-disinfection ( OR=0.241, 95%CI:0.144‒0.402) were influencing factors for KP contamination in environmental surface. From 2021 to 2023, the drug resistance rates of hospital environmental KP isolates showed an upward trend (P<0.001) to antibiotics such as ceftazidime and gentamicin. Furthermore, high drug resistance rates of KP (>90%) were observed to ciprofloxacin, levofloxacin, cefotaxime, ceftriaxone, and cefepime. ConclusionCRKP can be transmitted outward through the surfaces of objects in the patients’ surroundings, and the drug resistance situation is severe. In clinical settings, it is necessary to implement isolation measures for CRKP infection patients, to increase the frequency of disinfection for objects in their surroundings, to strengthen hand hygiene practices, and to use antibiotics appropriately.

Objective To explore the differences in stress distribution and stability of the planta pedis in the patients with unilateral and bilateral plantar fasciitis(PF)through plantar stress and center of pressure(COP)analysis.Methods A total of 100 patients with PF visiting in this hospital were enrolled,among them 50 cases were unilateral heel pain(unilateral heel pain group)and 50 cases were bilateral heel pain(bilateral heel pain).Meanwhile,50 healthy subjects were included(healthy group).In the health group and bilateral heel pain groups,the average stress value of both planta pedis surfaces of each subject was taken and named as the J0 group and H2 group,respectively.In the unilateral heel pain group,the plantar stress in 50 healthy feet and 50 affected feet were named as the J1 group and H1 group,respectively.The plantar pedis was divided into 10 regions for analysis and comparison[the first foot toe(T1),T2-5,the first-fifth metatarsal bones(M1-M5),the mid foot(MF),heel medial side(MH),heel lateral side(LH)].The subjects in 3 groups conducted the static and dynamic tests respectively,and the differences in plantar stress distribution and COP parameters among the J1,H1,H2 and J0 groups were compared respectively.Results In the static tests,the maximum pressure of the LH regions in the group J1 was increased when compared with the group J0,the contact area of LH regions in the group H1 was reduced when compared with the group J0,the maximum pressure of the M2 and M3 regions in the H1 group was increased when compared with the group J0,the contact areas of the MH and LH regions in the H2 group were decreased when compared with the group J0,the maximum pressure of the M1 region was increased when compared with the group J0,and the differences were statistically significant(P<0.05).In the dynamic tests,the maximum pressure of the T2-5 regions in the J1 group was increased when compared with the J0 group,the maximum pressure of the M3 region in the group H1 was increased when compared with the group J0,the maximum pressure of the M3 and M4 region in the group H2 was in-creased when compared with the group J0,and the differences were statistically significant(P<0.05).The COP 95%confidence ellipse area in the health group was the smallest,followed by the bilateral heel pain group,and finally the unilateral heel pain group,and the differences among 3 groups were statistically signifi-cant(P<0.05),there was also statistically significant difference between pairwise comparisons in 3 groups(P<0.05).Conclusion In the static condition,the pressure of the healthy heel and affected forefoot in the patients with PF is increased;while in the dynamic condition,the pressure of the toes of the healthy foot and forefoot of the affected foot in the patients with PF is also increased.The distribution of plantar stress in the patients with PF has larger difference compared with the healthy population,and the stability is poor.Meas-ures can be taken to improve the abnormal force on the foot,reduce pain and reduce the risk of falling.

Objective Understanding the population structure of mosquitoes in the drainage system of Minhang District,Shanghai,and exploring the physical prevention and control technology of mosquito traps with a Vazor mosquito repellent film in the drainage system.Methods A 500 mL water spoon was used to assist in visual inspection to investigate the breeding status of mosquito larvae in the drainage system.A carbon dioxide mosquito trap method was used to monitor adult mosquitoes around the ground drainage system,and the artificial hour method was used to monitor adult mosquitoes around the underground drainage system.Mosquito-repellent film was applied at a rate of 1 mL/m2 to the drainage system where mosquito larvae or pupae are found,and the breeding situation was observed and recorded.Results The positivity rate of mosquitoes breeding in the ground drainage system was 50%.The mosquito larvae in the drainage channels were primarily Aedes albopictus,whereas Ae.albopictus were primarily noted in the sewage wells.The proportions of Ae.albopictus and Culex pipiens pallens in the rainwater wells were similar,and the dominant mosquito species around the surface drainage system was Ae.Albopictus.The positive rate of mosquito breeding in the underground drainage system was 47%,with the dominant mosquito species being Cx.pipiens pallens(58.39%)followed by Ae.albopictus(41.6%).The dominant adult mosquito species around the drainage system were Cx.pipiens pallens(83%)followed by Ae.albopictus(11%).In terms of the effectiveness of mosquito-repellent water film,the mosquito breeding rates of the ground and underground drainage systems using mosquito-repellent water film decreased to 2.78%and 5%after 1 week of use,respectively,and then rebounded after the 3rd week.After a supplementary dose during the 5th week,the breeding rates returned to normal.No statistically significant differences were observed in the effect compared with the standard control group using 1%bisulfite granules;however,a statistically significant difference was noted compared with the blank control group without special treatment.Conclusions In the drainage system of Minhang District,Shanghai,mosquito breeding is severe,and variations exist in the dominant mosquito species in different environmental drainage facilities.The simultaneous use of mosquito-repellent films can effectively control mosquito breeding in drainage systems.

Objective To mine the risk signals of adverse drug events(ADEs)related to lecanemab through the U.S.Food and Drug Adminstration Adverse Event Reporting System(FAERS)database,to provide a reference for the safe clinical use of lecanemab.Methods Data on adverse events related to lecanemab from the fourth quarter,2010 to the second quarter 2024 in the FAERS were collected.Potential ADE signals were mined using the reporting odds ratio(ROR)method,Medicines and Healthcare Products Regulatory Agency(MHRA)method,Bayesian confidence propagation neural network(BCPNN)method and multi-item gamma Poisson shrinker(MGPS)method.The top 30 ADEs in terms of report frequency and signal strength,as well as ADEs categorized by system organ class(SOC),were statistically analyzed.Results A total of 868 adverse event reports related to lecanemab were collected,involving 1,986 instances of ADEs with 38 related ADE identified,the proportion of serious ADEs was 23.39％,and 87.15％of ADEs occurred in the first 3 months after the initiation of the drug.The top 30 PT signals in reported cases were headache,chills,fatigue,effusion type amyloid-related imaging abnormalities(ARIA-E),hemorrhage-type amyloid-related imaging abnormalities(ARIA-H),and so on.The top 30 signals in terms of signal intensity mainly included ARIA-E,ARIA-H,brain fog,infusion-related reactions.ADEs related to nervous system diseases were the most common.Fifteen new suspected or serious ADEs not recorded in the instructions were discovered,such as brain fog,formication,status epilepticus.Conclusion Risk assessment of patients'medication should be conducted before clinical use of lecanemab,especially in the first 3 months of the medication period,focus should be placed on monitoring common ADEs,such as ARIA-E,ARIA-H,infusion-related reactions.Attention also needs to be paid to the newly discovered suspected ADEs,to ensure the patients'medication safety.

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged