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.

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

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.

This study systematically collated and textual researched realgar from aspects such as name,origin,and quality by consulting ancient herbal texts,classic medical books,and modern literature.The textual research shows that current herbal works all take"realgar"as the official name,with aliases including"Huangshi shi","Shihuang","Tianyang shi","Jiguan shi","Xunhuang","Chouhuang",and"Mingxiong",etc.Ancient herbal records indicate that Xunhuang,Chouhuang,and Shuiku Realgar are all Realgar,while Orpiment is its associated mineral.In ancient times,the main production areas of Realgar were in Gansu,with outputs also seen in Shandong and Hunan.Nowadays,it is mainly produced in Hunan,Guizhou,Hubei,Gansu,Yunnan,Sichuan and other regions.Ancient herbal works mentioned characteristics like"cockscomb color","non-stinky","solid","red and bright"in their quality evaluation,while modern herbal works mostly evaluate its quality by color and texture,such as"red color","large blocks","brittle texture","glossy".The traditional efficacy of Realgar is to dry dampness,kill insects,detoxify various poisons,treat sores and activate blood.Modern studies have shown it also has anti-tumor,antibacterial and antiviral effects.Processing methods in past dynasties included water grinding,vinegar processing,refining,etc.,and currently,water grinding and acid water grinding are commonly used.This paper observed the properties of Realgar,detected the content of As?S?,and analyzed the microscopic characteristics and far-infrared spectral characteristics of qualified batches of Realgar.It was finally found that the As?S? content of qualified batches of Realgar was all more than 90%;under the scanning electron microscope,it showed massive shape,uniform distribution,obvious particles,and no agglomeration;a small amount of associated mineral Orpiment crystals were observed under the polarizing microscope;the characteristic peaks of Realgar(343-344 cm?1,224-225 cm?1,372-374 cm?1,367-369 cm?1,359 cm?1,207-208 cm?1,193-194 cm?1,168-170 cm?1)and Orpiment(390 cm?1,380 cm?1,347 cm?1,311 cm?1,300 cm?1,201 cm?1,182 cm?1,158 cm?1 and 139 cm?1)were determined."Red color and glossy"can be used as property references,"Realgar is a sulfide mineral of the Realgar family,with the main chemical component As?S?,associated with Orpiment"can be used as origin references,and"Shimen in Hunan,Wanshan in Guizhou,Yunnan,Gansu,Sichuan"can be used as production area references,which are consistent with the results of herbal textual research.This study provides a basis for the identification and analysis of Realgar,with a view to better guiding clinical medication and resource utilization.

Objective To analyze the effects of irbesartan(IBN)regulating the stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)pathway on proliferation,migration,and radiosensitivity of lung cancer cells.Methods Human lung cancer A549 cells were randomly divided into the A549 group(without treatment),radiation group(4 Gy X-ray radiation),IBN group(1 μmol/L IBN treatment for 24 hours),IBN+radiation group(1 μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation),pcDNA3.1 group(transfected with pcDNA3.1+1 μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation),and SDF-1 group(transfected with pcDNA3.1 SDF-1+1 μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation).The cell viability,colony formation,apoptosis,and migration of each group were observed.The leakage rate of lactate dehydrogenase(LDH)and Ang Ⅱ levels in cells were detected.Immunofluorescence method was applied to analyze the number of γH2AX focal points of cells in each group.Western blot was applied to detect the expression of proliferation and apoptosis related proteins and SDF-1/CXCR4 pathway related proteins.Results Both radiation and IBN treatment inhibited the proliferation and migration of A549 cells,promoted cell apoptosis,upregulated the number of γH2AX focal points and LDH leakage rate,upregulated the expression of Caspase-3,Bax,and Caspase-7,and downregulated the level of Ang Ⅱand expression of SDF-1,CXCR4,Bcl-2 and PCNA(P<0.05).The combined treatment of radiation and IBN further enhanced the changes of the above indicators(P<0.05).And SDF-1 treat-ment effectively reversed the effects of radiation and IBN treatment on the changes of the above indicators(P<0.05).Conclusion IBN can limit proliferation and migration of lung cancer cells,and increase radiosensitivity by inhibiting the SDF-1/CXCR4 pathway.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

Objective To analyze the effects of irbesartan(IBN)regulating the stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)pathway on proliferation,migration,and radiosensitivity of lung cancer cells.Methods Human lung cancer A549 cells were randomly divided into the A549 group(without treatment),radiation group(4 Gy X-ray radiation),IBN group(1 μmol/L IBN treatment for 24 hours),IBN+radiation group(1 μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation),pcDNA3.1 group(transfected with pcDNA3.1+1 μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation),and SDF-1 group(transfected with pcDNA3.1 SDF-1+1 μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation).The cell viability,colony formation,apoptosis,and migration of each group were observed.The leakage rate of lactate dehydrogenase(LDH)and Ang Ⅱ levels in cells were detected.Immunofluorescence method was applied to analyze the number of γH2AX focal points of cells in each group.Western blot was applied to detect the expression of proliferation and apoptosis related proteins and SDF-1/CXCR4 pathway related proteins.Results Both radiation and IBN treatment inhibited the proliferation and migration of A549 cells,promoted cell apoptosis,upregulated the number of γH2AX focal points and LDH leakage rate,upregulated the expression of Caspase-3,Bax,and Caspase-7,and downregulated the level of Ang Ⅱand expression of SDF-1,CXCR4,Bcl-2 and PCNA(P<0.05).The combined treatment of radiation and IBN further enhanced the changes of the above indicators(P<0.05).And SDF-1 treat-ment effectively reversed the effects of radiation and IBN treatment on the changes of the above indicators(P<0.05).Conclusion IBN can limit proliferation and migration of lung cancer cells,and increase radiosensitivity by inhibiting the SDF-1/CXCR4 pathway.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

This study systematically collated and textual researched realgar from aspects such as name,origin,and quality by consulting ancient herbal texts,classic medical books,and modern literature.The textual research shows that current herbal works all take"realgar"as the official name,with aliases including"Huangshi shi","Shihuang","Tianyang shi","Jiguan shi","Xunhuang","Chouhuang",and"Mingxiong",etc.Ancient herbal records indicate that Xunhuang,Chouhuang,and Shuiku Realgar are all Realgar,while Orpiment is its associated mineral.In ancient times,the main production areas of Realgar were in Gansu,with outputs also seen in Shandong and Hunan.Nowadays,it is mainly produced in Hunan,Guizhou,Hubei,Gansu,Yunnan,Sichuan and other regions.Ancient herbal works mentioned characteristics like"cockscomb color","non-stinky","solid","red and bright"in their quality evaluation,while modern herbal works mostly evaluate its quality by color and texture,such as"red color","large blocks","brittle texture","glossy".The traditional efficacy of Realgar is to dry dampness,kill insects,detoxify various poisons,treat sores and activate blood.Modern studies have shown it also has anti-tumor,antibacterial and antiviral effects.Processing methods in past dynasties included water grinding,vinegar processing,refining,etc.,and currently,water grinding and acid water grinding are commonly used.This paper observed the properties of Realgar,detected the content of As?S?,and analyzed the microscopic characteristics and far-infrared spectral characteristics of qualified batches of Realgar.It was finally found that the As?S? content of qualified batches of Realgar was all more than 90%;under the scanning electron microscope,it showed massive shape,uniform distribution,obvious particles,and no agglomeration;a small amount of associated mineral Orpiment crystals were observed under the polarizing microscope;the characteristic peaks of Realgar(343-344 cm?1,224-225 cm?1,372-374 cm?1,367-369 cm?1,359 cm?1,207-208 cm?1,193-194 cm?1,168-170 cm?1)and Orpiment(390 cm?1,380 cm?1,347 cm?1,311 cm?1,300 cm?1,201 cm?1,182 cm?1,158 cm?1 and 139 cm?1)were determined."Red color and glossy"can be used as property references,"Realgar is a sulfide mineral of the Realgar family,with the main chemical component As?S?,associated with Orpiment"can be used as origin references,and"Shimen in Hunan,Wanshan in Guizhou,Yunnan,Gansu,Sichuan"can be used as production area references,which are consistent with the results of herbal textual research.This study provides a basis for the identification and analysis of Realgar,with a view to better guiding clinical medication and resource utilization.

OBJECTIVE: Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS: Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS: Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals ; Psoriasis/chemically induced* ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Disease Models, Animal ; Cupping Therapy/methods* ; Signal Transduction ; Imiquimod ; Ion Channels/genetics* ; Male ; Mechanotransduction, Cellular