Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome， whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms. As an important pathway of anti-inflammatory and anti-oxidative stress， the nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathway is very important in the occurrence and development of sepsis-induced lung injury. This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine （TCM） to ameliorate sepsis- induced lung injury. It has been found that 14 kinds of TCM effective ingredients （including five types of compounds： flavonoids， terpenes， alkaloids， saponins， phenols） and 6 kinds of compound preparations （including three types of formulas： heat-clearing and detoxifying formulas， purgative formulas for promoting bowel movement， and formulas for reinforcing vital qi and consolidating the constitution） can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1， heme oxygenase-1， antioxidant response element and AMP-activated protein kinase， thereby alleviating sepsis-induced lung injury.

Objective: To investigate the clinical efficacy and safety of pudendal nerve modulation (PNM) in the treatment of female pudendal neuralgia (PN)，so as to promote the clinical application of this technique. Methods: A retrospective analysis was conducted on 20 female PN patients who failed conservative treatment at Gongli Hospital during Nov.2020 and Oct.2023.All patients underwent simultaneous PNM and sacral nerve modulation (SNM) with the assistance of 3D printing navigation.Dual-stage test electrodes for PNM and SNM were implanted，followed by alternate therapeutic trial for each modality.Secondary conversion rates and longitudinal outcomes，including visual analogue score (VAS)，patient health questionnaire-9 (PHQ-9)，and quality of life (QoL) scores were compared preoperatively，post-stage Ⅰ，and at 3，6，and 12 months post-stage Ⅱ. Results: All operations were successful.After the trial phase，the secondary conversion rate for PNM was significantly higher than that for SNM; 16 patients (16/20，80%) chose the second-phase PNM implantation surgery，3 (3/20，15%) chose second-phase SNM implantation，and 1 (1/20，5%) had electrodes removed due to ineffective results from both trials.Further assessment revealed that the improvements in VAS，PHQ-9，and QoL scores for PNM patients were significantly better than those for SNM patients after the first phase of surgery and at 3，6 and 12 months after the second-phase conversion (P<0.05).No complications such as electrode migration or infection were observed during the follow-up of 12-15 months. Conclusion: PNM provides more effective relief of pain symptoms and improvements in depressive states for female PN patients compared to SNM.With the assistance of 3D printing navigation，the operation is simple and safe，and offers stable therapeutic effects.It is worthy of clinical promotion and application.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl₄） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl₄ was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg^-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G₀/G₁ phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G₀/G₁ phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G₀/G₁ phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.