OBJECTIVE To investigate the potential mechanism by which Juanxiao decoction improves bronchial asthma （hereinafter referred to as “asthma”） based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome signaling pathway. METHODS Female SD rats were randomly assigned to normal group， model group and Juanxiao decoction low-， medium- and high-dose groups （0.36， 0.72 and 1.44 g/kg， calculated based on crude drug weight）， as well as positive control group （Dexamethasone acetate tablets， 0.2 mg/kg）， with 10 rats in each group. Except for the normal group， asthma models were established in the remaining groups via intraperitoneal injection of ovalbumin combined with aluminum hydroxide， followed by nebulized inhalation of ovalbumin. On day 14 of the experiment， rats in each group received intragastric administration of the corresponding solution or normal saline， once a day， for 7 consecutive days. Following the final administration， the following parameters were measured in each group： lung function indexes （forced vital capacity， forced expiratory volume in 0.3 second， peak expiratory flow）， serum levels of inflammatory markers （interleukin-1β， interleukin- 18）， and the percentages of inflammatory cells （lymphocytes， eosinophils， neutrophils） in bronchoalveolar lavage fluid. Histopathological changes in lung tissue were observed， and the protein and mRNA expressions of nuclear factor-kappa B （NF- κB）， NLRP3 and caspase-1 in lung tissue were detected. RESULTS Compared with the normal group， pathological changes such as alveolar wall thickening and inflammatory cell infiltration were observed in rats in the model group. All pulmonary function indicators were significantly reduced in rats in the model group and the administration groups. The levels of inflammatory markers， the percentages of inflammatory cells， and the protein and mRNA expressions of NF-κB， NLRP3 and caspase-1 were significantly elevated or up-regulated （P＜0.05）. Compared with the model group， pathological changes in rats in each dosage group of Juanxiao decoction were significantly alleviated， and all quantitative indicators showed dose-dependent improvements （P＜0.05）. CONCLUSIONS Juanxiao decoction can reduce airway inflammatory responses in asthmatic rats， alleviate lung function impairment， and improve pathological changes such as inflammatory cell infiltration. Those effects may be related to the inhibition of the NLRP3 inflammasome signaling pathway.

ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase （MAPK） signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model ， dapagliflozin （1.6 mg·kg^-1）， and Yishen Huashi granules （4.7 g·kg^-1）， and db/m mice were used as the control group. The general conditions of mice were observed， and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio （ACR） were measured at weeks 0 and 12 of administration. After 12 weeks of treatment， the levels of serum creatinine （SCr）， blood urea （UREA）， triglycerides （TG）， total cholesterol （TC）， and low density lipoprotein （LDL） were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining， Periodic acid-Schiff （PAS） staining， Mallory staining， and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 （MCP-1） and CC chemokine receptor-2 （CCR2） in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38， phospho-p38 （p-p38）， MCP-1， and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38， p38， MCP-1， and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows： negative control， high glucose（30 mmol·L^-1）， Yishen Huashi granule-containing serum， and SB203580. After 48 h of cell culture in each group， RNA were extracted and the levels of MCP-1， and CCR2 mRNA were determined by Real-time PCR，proteins were extracted and the levels of p38， p-p38， MCP-1， and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment， other groups had higher body weight， blood glucose level， 24 h urinary protein， and ACR than the control group （P<0.05，P<0.01）. After 12 weeks of treatment， compared with the model group， the Yishen Huashi granules group showed improved general conditions， a decreasing trend in body weight， lowered levels of blood glucose， 24-h urinary protein， and ACR （P<0.01）， reduced SCr and UREA （P<0.01）， and declined levels of TC， TG， and LDL （P<0.05，P<0.01）. Compared with the model group， the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover， the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01）， reduced positive expression of p-p38， MCP-1， and CCR2 （P<0.01）， and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2 （P<0.05） in the renal tissue. The cell experiment showed that compared with the high glucose group， the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01） and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2（P<0.05，P<0.01）. ConclusionYishen Huashi granules can regulate glucose-lipid metabolism， reduce 24 h urinary protein and ACR， improve the renal function， alleviate the renal tubule injury caused by high glucose， and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.

ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 （ GRP78 ） / transcription factor C / EBP homologous protein （ CHOP ） signaling pathway （GRP78/CHOP） signaling pathway. MethodsFor the animal experiment， 10 12-week-old db/m mice were selected as a normal group， and 30 12-week-old db/db mice were randomly divided into a model group， a Shenkang injection group （15.6 mL·kg^-1）， and a dapagliflozin group （1.6 mg·kg^-1）. To observe the general condition of mice， fasting blood glucose， urinary albumin/urine creatinine （ACR）， and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment， mice were tested for fasting blood glucose， total cholesterol （TC）， triglyceride （TG）， low-density cholesterol （LDL）， ACR， 24 h urine protein quantification， blood creatinine （SCr）， and blood urea （UREA）. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein （Nephrin）， glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in renal tissue. Western blot was used to detect the expressions of GRP78， CHOP， Bcl-2， Bax， and Nephrin proteins， and Real-time polymerase chain reaction （Real-time PCR） was employed to detect the expressions of Nephrin， GRP78， CHOP， Bcl-2， and Bax mRNAs in renal tissue. ResultsBefore drug administration， compared with those in the normal group， the body mass of db/db mice was significantly increased， and blood glucose， 24 h urine protein quantification， and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group （P<0.01）. After 12 weeks of administration， compared with those in the model group， the general state of mice in the Shenkang injection group was significantly improved， and the body mass was decreased. The blood glucose was significantly reduced （P<0.01）， and blood lipids TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）. The 24 h urine protein quantification and ACR were significantly decreased （P<0.05）， and SCr and UREA were significantly reduced （P<0.01）. Compared with those of the model group， the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells， reduction of inflammatory cell infiltration， and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78， CHOP， and Bax proteins were significantly reduced （P<0.01）， and the expressions of Nephrin and Bcl-2 proteins were significantly increased （P<0.01） in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased （P<0.05， P<0.01）， and the expressions of GRP78， CHOP， and Bax proteins were significantly decreased （P<0.05， P<0.01）. Real-time PCR results showed that the expressions of GRP78， CHOP， and Bax mRNAs were down regulated in the Shenkang injection group （P<0.01）， and the expressions of Nephrin and Bcl-2 mRNAs were up regulated （P<0.01）. ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway， which in turn ensures the integrity of glomerular filtration barrier， reduces the occurrence of proteinuria， improves renal function， and thus delays the progression of diabetic kidney disease.

ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 （ GRP78 ） / transcription factor C / EBP homologous protein （ CHOP ） signaling pathway （GRP78/CHOP） signaling pathway. MethodsFor the animal experiment， 10 12-week-old db/m mice were selected as a normal group， and 30 12-week-old db/db mice were randomly divided into a model group， a Shenkang injection group （15.6 mL·kg^-1）， and a dapagliflozin group （1.6 mg·kg^-1）. To observe the general condition of mice， fasting blood glucose， urinary albumin/urine creatinine （ACR）， and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment， mice were tested for fasting blood glucose， total cholesterol （TC）， triglyceride （TG）， low-density cholesterol （LDL）， ACR， 24 h urine protein quantification， blood creatinine （SCr）， and blood urea （UREA）. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein （Nephrin）， glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in renal tissue. Western blot was used to detect the expressions of GRP78， CHOP， Bcl-2， Bax， and Nephrin proteins， and Real-time polymerase chain reaction （Real-time PCR） was employed to detect the expressions of Nephrin， GRP78， CHOP， Bcl-2， and Bax mRNAs in renal tissue. ResultsBefore drug administration， compared with those in the normal group， the body mass of db/db mice was significantly increased， and blood glucose， 24 h urine protein quantification， and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group （P<0.01）. After 12 weeks of administration， compared with those in the model group， the general state of mice in the Shenkang injection group was significantly improved， and the body mass was decreased. The blood glucose was significantly reduced （P<0.01）， and blood lipids TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）. The 24 h urine protein quantification and ACR were significantly decreased （P<0.05）， and SCr and UREA were significantly reduced （P<0.01）. Compared with those of the model group， the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells， reduction of inflammatory cell infiltration， and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78， CHOP， and Bax proteins were significantly reduced （P<0.01）， and the expressions of Nephrin and Bcl-2 proteins were significantly increased （P<0.01） in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased （P<0.05， P<0.01）， and the expressions of GRP78， CHOP， and Bax proteins were significantly decreased （P<0.05， P<0.01）. Real-time PCR results showed that the expressions of GRP78， CHOP， and Bax mRNAs were down regulated in the Shenkang injection group （P<0.01）， and the expressions of Nephrin and Bcl-2 mRNAs were up regulated （P<0.01）. ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway， which in turn ensures the integrity of glomerular filtration barrier， reduces the occurrence of proteinuria， improves renal function， and thus delays the progression of diabetic kidney disease.

Objective To investigate the levels of gross α and gross β activities in different water types within a 40-kilometer radius around the Zhangzhou Nuclear Power Plant prior to its operation. Methods In 2018, drinking water samples were collected from the area surrounding the nuclear power plant during both the wet and dry seasons, including source water, treated water, tap water, and well water. The gross α and gross β activity concentrations were measured using a low-background α/β counter, followed by statistical analysis. Results A total of 80 water samples from different sources around the Zhangzhou Nuclear Power Plant were collected. The average gross α and gross β activity concentrations during the wet season were (0.110 ± 0.036) Bq/L and (0.643 ± 0.028) Bq/L, respectively, while those during the dry season were (0.124 ± 0.032) Bq/L and (0.624 ± 0.026) Bq/L, respectively. There were no significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for the overall sample set (P > 0.05). However, there were statistically significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for source water and well water (Z_wet = −2.005, −2.123; Z_dry = −1.943, −3.090; P < 0.05). Conclusion The radioactivity levels in different water types within various ranges around the Zhangzhou Nuclear Power Plant before its operation were determined. The measured activity concentrations were at the same level as those from previous investigations in other regions of Fujian Province.

Objective To investigate the impact of serine/threonine-protein kinase 1(AKT1)-mediated autophagy in hepatocellular carcinoma(HCC)cells on their sensitivity to 125I seed irradiation.Methods ① iProX database and STRING12.0 website were utilized to analyze the proteomic data of HCC before and after 125I seed irradiation to explore the differentially expressed proteins and associated functional connections.Meanwhile,The Cancer Genomics Atlas(TCGA)database was employed to analyze the relationship between AKT1 expression level and the survival of HCC patients.② Human HCC cell lines HUH7 and Hep3B were exposed to continuous irradiation from 125I radioactive seeds with an initial apparent activity of 0.8 mCi per seed for approximately 120 h,accumulating a total dose of 8 Gy,while the control cells were cultured under normal condition for 120 h.③ Autophagy inhibitor,chloroquine(CQ)and inducer,rapamycin(RAPA)were used to treat the HCC cells respectively to establish the CQ group and the RAPA group.The lentiviral transfection technique was employed to construct the HCC cells with overexpressed AKT1,namely the AKT1 group.The HCC cells treated in the same way were continuously irradiated with 125I seeds for 120 h to construct the CQ+125I group,the RAPA+125I group,and the AKT1+125I group.④The changes in microtubule-associated protein light chain 3(LC3),p62,AKT1 and p-AKT1 were detected by Western blotting.Cell immunofluorescence assay was employed to observe the expression of autophagy related proteins,such as LC3.The colony forming ability and apoptotic rate were detected with plate cloning assay and flow cytometry.Results ① Continuous irradiation with 125I seeds resulted in decreased expression of p62 and increased ratio of LC3Ⅱ/LC3Ⅰ(P＜0.05)when compared with the negative control(NC)group.Immunofluorescence assay revealed more green fluorescence spots of LC3.When compared with the 125I group,the CQ+125I group had significantly increased expression of p62(P＜0.01),decreased ratio of LC3Ⅱ/LC3Ⅰ(P＜0.01),lower apoptotic rate(P＜0.01),and more colony formations(P＜0.01).In contrast,the results in the RAPA+125I group were opposite to those of the CQ+125I group.② Analysis on the iProX database showed that the expression of AKT1 was decreased in the irradiated group,and analysis on the TCGA database indicated that high expression of AKT1 predicted a poor prognosis for HCC patients(P＜0.01).③After irradiation with 125I seeds,the expression of AKT1 at both the RNA and protein levels was decreased in the 125I group(P＜0.01).After overexpression of AKT1,the level of autophagy was decreased(P＜0.05).Irradiation of HCC cells with overexpressed AKT1 using 125I seeds could partially restore the level of autophagy.In the AKT1+125I group,the expression of AKT1,pAKT1 and p62 were all decreased,and the ratio of LC3Ⅱ/LC3Ⅰwas increased than the AKT1 group(P＜0.05).④ The apoptotic rate of the AKT1+125I group was lower than that of the 125I group(P＜0.05)and higher than that in the AKT1 group(P＜0.05).In HUH7 cells,the clonogenic ability of the AKT1+125I group was higher than that of the 125I group(P＜0.05).In Hep3B cells,the clonogenic ability of the AKT1+125I group was higher than that of the 125I group,and the clonogenic ability of the AKT1 group was higher than that of the NC group(P＜0.05).Conclusion 125I seed irradiation induce lethal autophagy in HCC cells by reducing the expression of AKT1,providing a new theoretical basis for the implantation of 125I radioactive seeds in the treatment of HCC.

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder characterized by recurrent episodes of skin and/or mucosal edema, with laryngeal edema posing a life-threatening risk. This paper reports the general conditions, diagnostic and therapeutic processes, and current status of 10 patients diagnosed with HAE at the First Affiliated Hospital of Kunming Medical University between October 2022 and March 2025. Eight cases were type 1 and two were type 2. Patient ages ranged from 17 to 55 years, with a median age at diagnosis of 36 years and a median age at onset of 17 years. The median diagnostic delay was 13.5 years, with the longest delay being 40 years and the shortest 4 years. Clinical presentations were diverse, primarily involving recurrent skin and/or mucosal edema. All 10 patients presented with upper respiratory tract mucosal edema, five cases exhibited prominent gastrointestinal edema accompanied by abdominal pain and distension. By reporting the clinical characteristics of 10 confirmed cases of HAE, this paper aims to provide a reference for clinicians in their diagnosis and treatment.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Objective To investigate the effect of progesterone receptor membrane component 1(PGRMC1)mediated autophagy on the sensitivity of liver cancer cells to 125I particles irradiation.Methods Hepatoma cell lines Huh7 and LM3 were exposed to different doses(0,2,4,6 and 8 Gy)of 125I particles,and cell autophagy was observed by transmission electron microscopy(TEM).Then,autophagy inhibitor chloroquine(CQ),agonist rapamycin(Rapa),and PGRMC1 inhibitor AG-205 were used respectively to verify that PGRMC1-mediated autophagy plays a key role in the sensitivity of hepatocellular carcinoma cells to 125I particle irradiation.Cell proliferation,colony formation and apoptosis were detected by CCK-8 assay,clonal formation test and flow cytometry,respectively.The expression levels of PGRMC1,microtubule-associated protein light chain 3-Ⅰ(LC3-Ⅰ),LC3-Ⅱ and p62 were detected by Western blotting.Results Different doses of 125I particles irradiation significantly decreased the proliferation and clonogenesis of Huh7 and LM3 cells(P＜0.05),and increased the apoptotic cells(P＜0.01),in a dose-dependent manner.Compared with the 0 Gy group,the ratio of LC3-Ⅱ/LC3-Ⅰ in Huh7 and LM3 cells was obviously increased,and the expression of p62 was significantly down-regulated in the 6 Gy group.The proliferation capacity and clonal formation ability of Huh7 and LM3 cells were decreased significantly,and their apoptotic cells were increased notably in the 6 Gy+CQ group than the 6 Gy group,while the above results were on the contrary in the 6 Gy+Rapa group.The 6 Gy+AG205 group had notably decreased LC3-Ⅱ/LC3-Ⅰ ratio in the Huh7 and LM3 cells,up-regulated p62 expression,reduced cell proliferation capacity and clone formation ability,and enhanced cell apoptosis when compared with the 6 Gy group,and the above results of the 6 Gy+PGRMC1 group were opposite.Conclusion Increment of PGRMC1 induced by 125I irradiation can promote autophagy,increase the proliferation and clonogenesis,and reduce the apoptosis in hepatocellular carcinoma cells.

Objective Scutellaria baicalensis stems and leaves glucuronic hydrolase(sbsl GUS)was used to enzymatically hydrolyze scutellarin in Erigeron breviscapus(Vant.)Hand.Mazz.to prepare scutellarein,and the high-purity scutellarein was obtained through separation and purification.Methods Orthogonal experiments were used to optimize the process parameters for the extraction of Erigeron breviscapus(Vant.)Hand.Mazz..Using the rate of enzymatic hydrolysis conversion of scutellarin as the index,the amount of enzyme,pH,temperature,time and antioxidant were investigated,and the preparation process parameters of scutellarein were optimized.Ethanol extraction,activated carbon decolorization,and fractional crystallization were used to purify the crude extract.Results The extraction process was determined to be:segments of Erigeron breviscapus were decocted twice with 10 times water for 1 hour each time.The preparation process of scutellarein was as follows:the amount of sbsl GUS extract and Erigeron breviscapus decoction was 1∶10 based on crude drugs,0.5%sodium metabisulfite was added,pH value was about 6.0,the temperature was about 45℃,and the time was 20 hours.The crude extract of scutellarein with the content more than 60%was obtained.The crude extract was purified by fractional crystallization,refluxed with 80%ethanol,decolorized with activated carbon,concentrated and crystallized,and the scutellarein extract with content more than 85%was obtained.Conclusion sbsl GUS enzymatic hydrolysis technology,which was used to prepare scutellarein,is simple and feasible.This study provides a new way for the manufacture of scutellarein.