ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis （KOA） and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization， which can effectively inhibit the progression of pathological inflammatory response， reduce the release of inflammatory pain mediators， and downregulate the protein expression level of transient receptor potential vanilloid 1 （TRPV1）， so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding， Sprague-Dawley （SD） rats were randomly divided into six groups： sham group， model group， celecoxib group， and high， medium， and low-dose synovitis granule groups （9.6， 4.8， 2.4 g·kg^-1）. The administration dose of celecoxib capsules was 20 mg·kg^-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10^th day of the experiment， each administration group was given intragastric administration at a dose of 10 mL·kg^-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold （PPT） to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay （ELISA） was performed to detect the tumor necrosis factor-α （TNF-α）， serum interleukin-1β （IL-1β）， and other pro-inflammatory cytokines in rat serum samples， as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor （NGF） and calcitonin gene-related peptide （CGRP）. Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin （HE） staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1， p38 mitogen-activated protein kinase （p38 MAPK）， and phosphorylated （p）-p38 MAPK in rat knee synovial tissues. Immunofluorescence （IF） was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group， the circumference and joint diameter of the right knee were markedly enlarged in the model group （P<0.01）， while PPTs of rats showed a significant reduction （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in rats' serum were significantly elevated （P<0.01）， and the synovial Krenn score was increased （P<0.01）. The Mankin score of cartilage tissue was increased （P<0.01）， and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated （P<0.01）. The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population （P<0.01）， and the percentage of M2 macrophages was decreased （P<0.01）. The M1/M2 macrophage ratio was significantly elevated （P<0.01）. Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced （P<0.01） compared with those of the model group， and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious （P<0.05）. The contents of IL-1β， CGRP， and NGF in the rats' serum in all administration groups were significantly reduced （P<0.05， P<0.01）， and the content of TNF-α in rats' serum was significantly reduced （P<0.01）. All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score （P<0.05， P<0.01） and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues （P<0.01）. The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased （P<0.01）. The percentage of M2 macrophages was increased （P<0.05）， and the M1/M2 ratio was decreased （P<0.01）. ConclusionHuamoyan granules can alleviate the inflammatory response of KOA， reduce the release of inflammatory pain mediators， and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway， thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.

Chaihu Guizhi Ganjiangtang was first recorded in the Treatise on Cold Damage （Shang Han Lun）. This prescription is composed of Bupleuri Radix， Scutellariae Radix， Cinnamomi Ramulus， Zingiberis Rhizoma， Trichosanthis Radix， Ostreae Concha， and Glycyrrhizae Radix et Rhizoma. It has the effects of soothing Lesser Yang， warming the spleen， and stimulating the generation of body fluid. It is mainly used to treat digestive tract diseases such as chronic cholecystitis （CC）， irritable bowel syndrome， and non-alcoholic fatty liver disease. Dyspepsia caused by CC presents a variety of gastrointestinal symptoms such as abdominal pain， poor appetite， postprandial fullness， aversion to greasy food， soft stool， and bitter mouth， being a type of biliary dyspepsia. In modern medicine， dyspepsia caused by CC is mainly managed by medical treatment and surgical treatment. Internal medicine mainly focuses on reducing inflammation， promoting the function of gallbladder， resolving stones， alleviating spasms， and relieving the pain for CC， demonstrating definite short-term efficacy but suffering from single effects， high recurrence rate， and poor compliance. Although surgical treatment can cure cholecystitis， it is accompanied by the increased incidence of adverse events such as abdominal pain， diarrhea， and dyspepsia. Modern clinical studies have confirmed that Chaihu Guizhi Ganjiangtang can significantly alleviate the symptoms such as abdominal pain and dyspepsia of CC patients. Pharmacological studies have found that Chaihu Guizhi Ganjiangtang mainly contains active ingredients such as Bupleuri Radix saponins， baicalin， cinnamaldehyde， gingerol， Trichosanthis Radix polysaccharide， Ostreae Concha polysaccharide， and Glycyrrhizae Radix et Rhizoma total flavonoids. Chaihu Guizhi Ganjiangtang can ameliorate the symptoms of dyspepsia caused by CC by inhibiting inflammatory responses， improving gallbladder contraction and gastrointestinal motility， regulating the bile acid-intestinal flora axis and the brain-gut axis， and modulating blood lipids through multiple targets. By reviewing the previous literature， this article summarizes the research progress in the treatment of dyspepsia caused by CC with Chaihu Guizhi Ganjiangtang and its main active ingredients as well as the pathogenesis of this disease and puts forward the shortcomings and improvement strategies for the current research. The review aims to provide a reference for the further research on Chaihu Guizhi Ganjiangtang in the treatment of dyspepsia caused by CC.

Functional dyspepsia （FD） is a prioritized disease category where traditional Chinese medicine （TCM） demonstrates distinct therapeutic advantages. The current western medicine treatment for FD is mainly based on proton pump inhibitors and prokinetic agents， with digestive enzymes， probiotics and antidepressants serving as adjuvant medication， yet such therapies still have certain limitations. TCM treatment for FD includes oral administration of Chinese herbal formulas and Chinese patent medicines， as well as external TCM therapies such as acupuncture and moxibustion， acupoint application， hot medicinal compress therapy， rubbing with ointment， medicinal iontophoresis， auricular acupoint therapy and tui na （Chinese medical massage）. The combined treatment of FD with integrated TCM and western medicine can significantly improve clinical effectiveness and reduce adverse reactions. The common mechanisms underlying the therapeutic effects of both TCM and western medicine revolve around the core pathological processes of FD， mainly focusing on restoring gastrointestinal motility， regulating the levels of brain-gut peptides， modulating intestinal microecology， and ameliorating inflammatory status. The differential mechanisms lie in the precise targeting feature of western medicine versus the holistic-regulating and multi-target characteristics of TCM， and the two approaches exert a synergistic effect to enhance efficacy. This paper proposes to leverage the advantages of TCM in holistic regulation and the strengths of western medicine in targeted treatment， so as to provide personalized and comprehensive treatment regimens for FD patients.

Objective To evaluate the effectiveness of schistosomiasis surveillance in Jiangsu Province during the stage moving from transmission control to transmission interruption, and to analyze the current risk and challenges, so as to provide the evidence for achieving the target of schistosomiasis elimination. Methods Schistosomiasis surveillance data were collected from Jiangsu Province from 2012 to 2024, and the endemic areas, Schistosoma japonicum infections in humans and livestock, Oncomelania hupensis snail distribution and implementation of integrated interventions were descriptively analyzed. In addition, the trends in areas with snails, seroprevalence of human S. japonicum infections and numbers of advanced schistosomiasis cases were assessed using a Joinpoint regression model. Results The endemic areas of schistosomiasis continued to shrink in Jiangsu Province from 2012 to 2024, with the number of schistosomiasis-eliminated counties (cities, districts) increasing from 53 (75.71%) to 63 (96.92%), and interruption of schistosomiasis transmission was achieved across the province. A total of 4 600 300 person-times were tested for serum antibodies against S. japonicum, with 28 719 person-times positive detected; and 616 500 person-times were tested S. japonicum infections among local residents in Jiangsu Province from 2012 to 2024, with only 3 egg-positives detected, and no egg-positives found since 2017. A total of 187 600 herd-times were tested for schistosomiasis in livestock, and no S. japonicum infections were found. O. hupensis snail survey was performed covering 1 018 408.97 hm², and a total of 35 556.35 hm² was found with snail-infested habitats, including 174.40 hm2 of emerging snail-infested habitats. A total of 1 102 800 O. hupensis snails were identified for S. japonicum infections, and no infections were found. The areas of snail-infested habitats appeared a tendency towards a rise in Jiangsu Province from 2019 to 2023 (APC = 23.67%, P < 0.05), and the actual areas of snail-infested habitats appeared a tendency towards a decline from 2012 to 2015 (APC = −22.77%, P < 0.05), and towards a rise from 2015 to 2023 (APC = 9.76%, P < 0.01). The seroprevalence of anti-S. japonicum antibodies appeared a tendency towards a decline among residents in Jiangsu Province from 2017 to 2023 (APC = −14.92%, P < 0.01). In addition, the number of newly diagnosed advanced schistosomiasis cases appeared a tendency towards a decline from 2012 to 2024 (APC = −12.02%, P < 0.01), and the numbers of advanced schistosomiasis patients requiring treatment showed a tendency towards a decline from 2012 to 2021 (APC = −10.56%, P < 0.01) and from 2021 to 2023 (APC = −20.06%, P < 0.01). Conclusions Great progresses had been achieved in schistosomiasis control in Jiangsu Province following transmission control, and transmission interruption had been achieved; however, there are still snail-infested habitats. High-intensity surveillance and integrated control are required to be maintained to advance the achievement of the target of schistosomiasis elimination in Jiangsu Province.

Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×10⁷/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.

ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

ObjectiveTo investigate the effects and underlying mechanisms of Shenqi Wenfei prescription （SQWF） on chronic obstructive pulmonary disease （COPD）. MethodsA rat model of COPD with lung Qi deficiency was established using lipopolysaccharide （LPS） combined with cigarette smoke. Forty-eight SD rats were randomly divided into a blank group， a model group， low-， medium-， and high-dose SQWF groups （2.835， 5.67， 11.34 g·kg^-1）， and a Yupingfeng group （1.35 g·kg^-1）. Drug administration began on day 29 after modeling and continued for 2 weeks. The general condition of the rats was observed， and the lung function in each group was assessed. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. The proportion of inflammatory cells in bronchoalveolar lavage fluid （BALF） was measured. Apoptosis in lung tissue was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） staining. The release level of lactate dehydrogenase （LDH） in BALF was detected by a microplate assay. Reactive oxygen species （ROS） levels in lung tissue were detected using fluorescent probes. The levels of malondialdehyde （MDA）， total superoxide dismutase （SOD）， and reduced glutathione （GSH） in BALF were measured by biochemical methods. Ultrastructural changes in lung cells were observed via transmission electron microscopy. Double immunofluorescence staining was performed to detect the expression of thioredoxin-interacting protein （TXNIP） and nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） in lung tissue. Western blot analysis was used to detect the protein expression of TXNIP， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific protease-1 （Caspase-1）， Caspase-1 p20， gasdermin D （GSDMD）， GSDMD N-terminal active fragment （GSDMD-N）， interleukin-1β （IL-1β）， and IL-18 in lung tissue. Serum IL-1β and IL-18 levels were measured by ELISA. ResultsCompared with the blank group， the model group showed lassitude， fatigue， tachypnea， and audible phlegm sounds， and lung function significantly declined （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were obvious. The level of inflammatory cells in BALF increased significantly （P0.05）. The number of TUNEL-positive cells increased （P0.01）. Levels of LDH， ROS， and MDA in BALF increased significantly （P0.01）， while GSH and SOD activities decreased significantly （P0.01）. Lung tissue cells showed irregular morphology， swollen mitochondria， disrupted cell membranes， and abundant vesicles， i.e.， pyroptotic bodies. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue were significantly elevated （P0.01）， and serum IL-1β and IL-18 levels also increased significantly （P0.01）. Compared with the model group， each medication group showed alleviation of qi deficiency symptoms and improved lung function （P0.01）. Pulmonary emphysema and inflammatory cell infiltration were reduced. Inflammatory cell levels decreased （P0.05）. The number of TUNEL-positive cells decreased significantly （P0.01）. Levels of LDH， ROS， and MDA decreased significantly （P0.05）， while GSH and SOD activities significantly increased （P0.01）. Morphological and structural damage in lung tissue was improved to varying degrees. Protein levels of TXNIP， NLRP3， ASC， Caspase-1， Caspase-1 p20， GSDMD， GSDMD-N， IL-1β， and IL-18 in lung tissue significantly decreased （P0.01）， and serum IL-1β and IL-18 levels also decreased significantly （P0.05）. ConclusionSQWF can improve lung function and alleviate inflammatory responses in COPD rats. Its mechanism may be related to regulating the ROS/TXNIP/NLRP3 pathway and inhibiting pyroptosis.

ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.