ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

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.

Objective To explore the application value of dual-phase dual-energy CT (DECT) perfusion imaging in preoperative lung function assessment of lung cancer patients. Methods Data were collected from patients with stageⅠA non-small cell lung cancer who underwent surgical treatment in the Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, from November 2022 to June 2024. All patients underwent DECT perfusion imaging and pulmonary function testing (PFT) before surgery. PFT observation indicators included ventilation function indicators such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC), 1-second rate (FEV1/FVC), maximal voluntary ventilation (MVV), and diffusion function indicators such as diffusing capacity for carbon monoxide (DLCO) and DLCO per liter of alveolar volume (DLCO/VA). The software eXamine was used to obtain quantitative parameters of DECT perfusion imaging, including volume parameters and perfusion parameters of both lungs and each lung lobe. The correlation between the volume parameters and perfusion parameters of both lungs and the ventilation and diffusion function indicators of the patients, as well as the differences in quantitative parameters of each lung lobe, was analyzed. Results The end-inspiration lung volume and biphasic volume difference were strongly positively correlated with FEV1 and FVC (r=0.636, r=0.682, r=0.614, r=0.624, P<0.001) and moderately positively correlated with MVV and DLCO (r=0.499, r=0.514, r=0.549, r=0.447, P<0.001); the end-expiration lung volume was weakly negatively correlated with DLCO/VA (r=−0.295, P=0.026); the volume ratio was positively correlated with FEV1, FVC, MVV, and MVV% (r=0.424, r=0.399, r=0.415, r=0.310, P<0.05); the end-inspiration iodine content was weakly positively correlated with DLCO/VA% (rs=0.292, P=0.030); the end-expiration iodine content was weakly positively correlated with FEV1, FVC, MVV, DLCO%, and DLCO/VA (r=0.307, r=0.299, r=0.295, r=0.366, r=0.320, P<0.05) and moderately positively correlated with DLCO (r=0.439, P<0.001); the end-inspiration iodine concentration was negatively correlated with FEV1, FVC, MVV, and MVV% (rs=−0.407, rs=−0.426, rs=−0.352, rs=−0.277, P＜0.05); the end-expiratory phase iodine concentration was moderately positively correlated with DLCO/VA (r=0.403, P=0.002); both the iodine concentration difference and the iodine concentration ratio were moderately positively correlated with FEV1, FEV1%, FVC, MVV, MVV% (P<0.05). The lung volume and iodine concentration ratio values were both highest in the left upper lung lobe and lowest in the right middle lung lobe; the differences in lung volume, lung volume ratio, intrapulmonary iodine content, and intrapulmonary iodine concentration were all highest in the lower lobes of both lungs and lowest in the middle lobe of the right lung. Conclusion Dual-phase DECT perfusion imaging can accurately assess overall lung function and quantify regional lung function.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Background The widespread use of herbicides has led to environmental contamination and has implications for human health. The liver is an important organ for the detoxification of environmental pollutants; however, studies on the association between herbicide exposure and liver function are limited. Objectives To investigate the association between baseline serum herbicide levels and changes in liver enzyme levels and liver enzyme abnormalities over a 5-year period in middle-aged and older adults. Methods This study was based on a nested case-control population of type 2 diabetes established in the Dongfeng-Tongji cohort, with a total of 1388 subjects included in this study and followed up for 5 years. Epidemiological data were collected through questionnaires, and baseline serum concentrations of three herbicides (metolachlor, propham, and acetochlor) were measured by gas chromatography-triple quadrupole mass spectrometry. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were detected at baseline and follow-up visits. The associations between baseline serum herbicide levels and changes in AST and ALT over 5 years were assessed using linear regression models with herbicide levels categorized into quartiles, adjusting for age, sex, education level, smoking status, drinking status, physical activity, body mass index, and new-onset type 2 diabetes occurred during follow-up. The relationship between baseline serum herbicide levels and the risk of liver enzyme abnormalities during follow-up was further analyzed using logistic regression models. Results The positive rates of metolachlor, propham, and acetochlor were all higher than 80%, and their spiked rates of recovery ranged from 73.46% to 106.77%. The mean ± standard deviation of the age of subjects at baseline was (62.7±7.6) years, with 34.1% being male. The median serum levels of metolachlor, propham, and acetochlor at baseline were 0.05, 0.16, and 0.03 ng·mL⁻¹, respectively. There was no significant difference in baseline serum herbicide levels between the normal and abnormal liver enzyme groups at follow-up (P >0.05). The baseline liver enzyme levels and the changes in AST and ALT over 5 years in those who developed abnormal liver enzymes were significantly higher than those in the normal liver enzyme group (P <0.05). The linear regression analysis showed that the changes in AST increased progressively over 5 years in the second, third, and fourth quartiles of propham compared to the lowest quartile group (the second quartile: b=1.49, 95%CI: 0.10, 2.87; the third quartile: b=1.52, 95%CI: 0.14, 2.90; the fourth quartile: b=1.69, 95%CI: 0.31, 3.08; P <0.05). The associations of serum metolachlor and acetochlor with changes in AST were not significant. Additionally, no significant relationships were found between the three serum herbicides and the changes in ALT over 5 years or the risk of liver enzyme abnormalities. Conclusion Serum propham levels in middle-aged and older adults are positively associated with changes in liver enzyme AST, which may have an effect on liver function. More studies are needed to provide scientific evidence for the association between herbicide exposure and liver function.

Autoimmune encephalitis（AE）refers broadly to a group of encephalitic disorders mediated by autoimmune mechanisms. AE is characterized by complex pathogeneses and diverse clinical manifestations，and there are still numerous challenges in the diagnosis and treatment of AE. With the development of frontier technologies such as vaccines，gene editing，and big data，new opportunities have emerged for transforming the diagnosis and treatment strategies for AE. Vaccines play a dual role in AE： on the one hand，they can prevent infections； on the other hand，they may trigger autoimmune responses through molecular mimicry. Emerging nanovaccine technologies are expected to achieve safer and more effective immunomodulation. Gene editing techniques，especially the CRISPR-Cas9 system，have shown potential in targeted regulation of the function of immune cells and repair of nervous tissue，which provides new pathways for precise intervention in the treatment of AE. The application of big data technologies，including artificial intelligence，natural language processing，and deep learning，has promoted the early diagnosis of AE and the development of individualized treatment regimens. This article reviews the research advances and clinical prospects of these cutting-edge technologies in AE，in order to provide insights and references for the development of precision medicine，interdisciplinary collaboration，and future treatment strategies for AE.

Mendel established the laws and laid the foundation of modern genetics through his famous hybridization experiments on seven pairs of classic traits in the garden pea (Pisum sativum). However, the molecular bases underlying these traits have only come into sharp focus in recent years. Leveraging advances in traditional map-based cloning, TILLING, long-read resequencing, population genetics, and GWAS, this article synthesizes current knowledge of ten genes governing seven traits—plant height, seed shape, flower color, seed color, pod color, pod morphology, and flower position—by summarizing each gene’s identity, chromosomal localization, and functional pathway. For plant height, the classical Le locus corresponds to PsGA3ox1, which encodes a gibberellin 3β-hydroxylase. Mutations at Le impede the biosynthesis of the bioactive hormone GA₁, and the resulting deficiency leads to a dwarf or reduced-stature phenotype. Seed shape is determined by R, identified as PsSBEI (starch-branching enzyme I). Insertion of a transposable element into R restricts amylopectin synthesis, perturbing endosperm starch architecture and resulting in the wrinkled seeds noted by Mendel. Flower color is specified by the coordinated action of A (a bHLH transcription factor) and A2 (a WD40 scaffold). Together, they assemble the canonical MYB-bHLH-WD40 (MBW) regulatory complex, which co-activates structural genes in the anthocyanin pathway to determine pigment accumulation and floral hue. Seed color is governed by I, which encodes PsSGR (STAY-GREEN), a magnesium dechelatase that catalyzes a key step in chlorophyll catabolism. Loss-of-function alleles at I block chlorophyll degradation, yielding “stay-green” seeds in which chlorophyll persists beyond normal developmental stages. Pod coloration maps to Gp, corresponding to ChlG (chlorophyll synthase). Either direct loss of ChlG function or readthrough-fusion transcriptional interference caused by a large upstream deletion suppresses chlorophyll biosynthesis in developing pods, resulting in the yellow-pod phenotype. Pod morphology depends on two convergent regulatory pathways. The P gene, PsCLE41, signals through the P-PXY-WOX/NAC axis to promote vascular differentiation and secondary-wall programs, while V encodes PsMYB26, a transcription factor that drives secondary wall thickening in fiber cells. Acting in concert, these modules ensure robust secondary-wall deposition in the fiber layer lining the inner pod wall; disruption of either component compromises wall thickening and leads to pleated or wrinkled pods. Flower position (inflorescence determinacy at the shoot apex) is controlled by FA, identified as PsCIK, which participates in the CLAVATA-WUSCHEL (CLV-WUS) feedback circuit that maintains shoot apical meristem homeostasis. Mutations in FA destabilize this self-regulatory loop and promote terminal flowers at the apex. The expressivity of this determinacy phenotype is further modulated by a recessive modifier, Mfa, which fine-tunes the outcome in the fa background. Across these loci, convergent evidence highlights the central role of structural variation in generating the classical Mendelian phenotypes. Building on this clarified molecular landscape, we outline practical implications for quality improvement and the deliberate “design” of traits. Looking ahead, we envisage a next generation of legume genetic improvement anchored on three mutually reinforcing pillars: high-quality reference genomes to deliver contiguous, structurally faithful assemblies; comprehensive pan-genomes to capture presence/absence variation and structural polymorphism across germplasm; and precise gene editing to target coding, regulatory, and structural features alike. Together, these tools chart a path toward mechanism-based breeding, enabling purposeful, design-driven trait improvement in peas and, by extension, other legumes.

INTRODUCTION: The aim of this study was to elucidate the epidemiology and distribution of hand fractures in Singapore. METHODS: A total of 701 hand fractures in 596 patients aged 21 years and above from a single centre were reviewed from 2010 to 2011. Details regarding the patient demographics, occupation, mechanism of injury, associated injuries and treatment were obtained. RESULTS: Hand fractures were particularly significant in patients between the ages of 21 and 40 years 58.9% of the total cases. The relative risk of hand fractures in males was 5.5 times greater than that in females. The majority of hand fractures occurred at the workplace (47.7%), with crush injury being the main mechanism of injury (33.6%). The most common locations of hand fracture were the little finger ray (31.2%) and distal phalanges (37.7%). There were 170 cases that underwent surgical fixation, which accounted for 24.3% of all fractures. Fixation rate was similar for both closed and open fractures but was significantly higher in the proximal and middle phalanges compared to the distal phalanx and metacarpal ( P < 0.001). With regards to surgical fixation methods, wires were commonly used in either tuft fractures (100.0%) or intra-articular fractures (69.9%), whereas plates and screws were commonly used in shaft fractures (65.5%). CONCLUSION The most significant population that sustained hand fractures in Singapore are young to middle-aged males who are skilled manual workers. The most commonly involved ray and location of hand fractures are the little finger ray and the distal phalanges, respectively, as they are in a relatively more exposed location.
Humans ; Singapore/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Fractures, Bone/surgery* ; Hand Injuries/surgery* ; Young Adult ; Aged ; Hand Bones/injuries* ; Retrospective Studies ; Fracture Fixation, Internal

The present study aimed to explore whether hydrogen sulfide (H₂S) improved hypoxic pulmonary hypertension (HPH) in rats by inhibiting aerobic glycolysis-pyroptosis. Male Sprague-Dawley (SD) rats were randomly divided into normal group, normal+NaHS group, hypoxia group, and hypoxia+NaHS group, with 6 rats in each group. The control group rats were placed in a normoxic (21% O₂) environment and received daily intraperitoneal injections of an equal volume of normal saline. The normal+NaHS group rats were placed in a normoxic environment and intraperitoneally injected with 14 μmol/kg NaHS daily. The hypoxia group rats were placed in a hypoxia chamber, and the oxygen controller inside the chamber maintained the oxygen concentration at 9% to 10% by controlling the N₂ flow rate. An equal volume of normal saline was injected intraperitoneally every day. The hypoxia+NaHS group rats were also placed in an hypoxia chamber and intraperitoneally injected with 14 μmol/kg NaHS daily. After the completion of the four-week modeling, the mean pulmonary artery pressure (mPAP) of each group was measured using right heart catheterization technique, and the right ventricular hypertrophy index (RVHI) was weighed and calculated. HE staining was used to observe pathological changes in lung tissue, Masson staining was used to observe fibrosis of lung tissue, and Western blot was used to detect protein expression levels of hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate kinase isozyme type M2 (PKM2), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), GSDMD-N-terminal domain (GSDMD-N), Caspase-1, interleukin-1β (IL-1β) and IL-18 in lung tissue. ELISA was used to detect contents of IL-1β and IL-18 in lung tissue. The results showed that, compared with the normal control group, there were no significant changes in all indexes in the normal+NaHS group, while the hypoxia group exhibited significantly increased mPAP and RVHI, thickened pulmonary vascular wall, narrowed lumen, increased collagen fibers, up-regulated expression levels of aerobic glycolysis-related proteins (HK2 and PKM2), up-regulated expression levels of pyroptosis-related proteins (NLRP3, GSDMD-N, Caspase-1, IL-1β, and IL-18), and increased contents of IL-1β and IL-18. These changes of the above indexes in the hypoxia group were significantly reversed by NaHS. These results suggest that H₂S can improve rat HPH by inhibiting aerobic glycolysis-pyroptosis.
Animals ; Rats, Sprague-Dawley ; Male ; Hypertension, Pulmonary/metabolism* ; Glycolysis/drug effects* ; Hydrogen Sulfide/therapeutic use* ; Hypoxia/complications* ; Rats ; Pyroptosis/drug effects*