ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C （SFTPC） and lung injury induced by chronic intermittent hypoxia （CIH） and the mechanism of action. MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups： a normoxia group， a CIH group， and low-， medium-， and high-dose Buzhong Yiqitang groups， with eight mice in each group. During the modeling， mice in the normoxia group were housed under standard oxygen concentrations， while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session， mice in the low-， medium-， and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses （8.1， 16.2， 32.4 g·kg^-1·d^-1 of crude drug， respectively）， while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung tissue were evaluated using hematoxylin-eosin （HE） staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. Protein expression of SFTPC， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， protein kinase R-like endoplasmic reticulum kinase （PERK）， phosphorylated PERK （p-PERK）， eukaryotic initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， activating transcript factor 4 （ATF4）， and CCAAT/enhancer-binding protein homologous protein （CHOP） in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue. ResultsCompared to those in the normoxia group， mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels increased， while SFTPC expression in lung tissue was reduced （P<0.05， P<0.01）. The rate of apoptotic cells in lung tissue increased， and the expression of endoplasmic reticulum stress markers p-PERK， p-eIF2α， ATF4， and CHOP was upregulated （P<0.05， P<0.01）. Compared with the CIH group， Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels were decreased， and lung tissue SFTPC expression was recovered （P<0.05， P<0.01）. The apoptotic rate of lung tissue cells was significantly reduced， with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression （P<0.05， P<0.01）. Activation and expression of p-PERK， p-eIF2α， ATF4， and CHOP were also decreased （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion， which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

Objective: To understand the dynamic temporal evolution pathways of Internet addiction among university students and to identify the core driving nodes, so as to provide theoretical evidences for the precise implementation of targeted interventions. Methods: Using a convenient cluster sampling method, a total of 1 066 full time freshmen and sophomores were recruited from three universities in Guizhou, Jiangxi, and Guangdong Provinces for a follow up survey (T1:January-March 2024; T2:January-March 2025). The Revised Chen Internet Addiction Scale (CIAS-R) was employed to assess the status of Internet addiction among university students, and cross sectional as well as cross lagged panel network models were constructed to analyze Internet addiction and its multidimensional influencing factors. Results: The T1 network comprised 19 nodes and 114 non zero edges, while the T2 network comprised 19 nodes and 126 non zero edges. Cross sectional network analysis revealed the strongest association between "insufficient sleep" and "daytime fatigue"; the core nodes were "first thought upon waking for going online" and "feeling low after disconnection" (characteristics of psychological dependence) at T1, while the core nodes shifted to "impaired health" and "excitement when online" (characteristics of functional impairment and addictive psychodynamic features) at T2. Cross lagged network analysis further indicated that "reduced leisure" directly predicted "sleep compression", and a bidirectional relationship was observed between "needing more time to achieve satisfaction" and "academic decline". Conclusions Internet addiction among university students exhibits dynamic evolutionary characteristics. Stage specific targeted interventions focusing on core driving nodes are needed, integrating behavioral regulation and academic support to break the vicious cycle and enhancing the ability to cope with real life demands.

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

Objective To investigate the dyadic coping experience of patients undergoing cancer surgery and their spouses.Methods Sixteen cancer patients who were initially diagnosed with cancer and underwent cancer surgery in a general hospital in Henan province as well as and their spouses were selected as the study subjects by objective sampling method.All the patients and their spouses were included in the postoperative follow-up for dyadic coping experiences though a 3 months interview.The acquired data were summarised and analysed by Colaizzi's phenomenological method to identify relevant themes.Results A total of eight themes were identified,including three themes over the phase of confirmed diagnosis,strong stress response,coping with stress alone and consistent attitude towards seeking medical treatment;two themes over the perioperative phase,lack of coping ability and change in relationship;and three themes over the phase of home recovery,lack of disease information,poor communication skills and post-trauma growth of both patient and spouse.Conclusions The dyadic coping experience of patients who undergo cancer surgery and their spouses varies with the stages across the treatment.Therefore,medical staff should offer targeted nursing care according to the dyadic coping experience at different stages,hence to improve the physical and mental health of the cancer patients and their spouses.

OBJECTIVE Based on the G protein-coupled bile acid receptor(TGR5)/nucleotide binding oligomerization domain-like receptor 3(NLRP3) signaling pathway, to explore the mechanism of Huoxue Qingjieling in improving the inflammatory response of rats with nonalcoholic steatohepatitis(NASH). METHODS A total of 70 male SD rats were randomly divided into 5 groups, 20 rats in the control group, 20 rats in the model group, 10 rats in each of the atorvastatin positive drug group, the high-dose and low-dose groups of Huoxue Qingjieling. The control group was given normal feed, and the rest of the groups were given high-fat diet. Through model evaluation, it was determined that the NASH rat model was successfully established at the end of the 20th week. After successful modeling, the control group and the model group were given with normal saline by intragastric administration, the atorvastatin positive drug group, and the high and low dose groups of Huoxue Qingjieling were given corresponding drugs once a day for 4 weeks. At the end of the 24th week, the rats were killed, and the changes of body weight, wet liver weight and liver index was calculated. The serum was taken to test the triglyceride(TG), total cholesterol(TC), alanine aminotransferase(ALT), and aspartic acid aminotransferase(AST) levels by automatic biochemical analyzer. Pathological changes of liver tissues were observed by HE staining and oil red O staining. The expression levels of TGR5 and NLRP3 proteins were detected by Western blotting and immunofluorescence staining. ELISA detected the content of interleukin-18(IL-18) and interleukin-1β(IL-1β) in liver tissue. RESULTS Huoxue Qingjieling could significantly improve the general state of NASH rats. Every dose group could significantly reduce the body weight, liver wet weight and liver index of rats(P<0.01), and TG, TC content and ALT, AST activity levels of serum significantly decreased(P<0.01). The pathological results showed that Huoxue Qingjieling could significantly improve liver steatosis, inflammation and balloon-like. The expression of TGR5 protein was significantly increased(P<0.01), the expression of NLRP3 protein and the content of IL-18, IL-1β were significantly decreased(P<0.01, P<0.05). CONCLUSION Huoxue Qingjieling can significantly improve the state of NASH rats, inhibit liver steatosis and inflammation, and its mechanism may be closely related to the inhibition of TGR5/NLRP3 signaling pathway.

Objective To explore the effect of miR-296-3p on hepatic fibrosis induced by bile duct ligation(BDL)in rats.Methods 25 SD rats were randomly divided into sham group,model(BDL)group,NC adv group,miR-296-3p adv group and miR-296-3p sponge adv group,with 5 rats in each group.The pathological changes were ob-served in rat liver tissue via HE,Masson and Sirius Red staining;the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBIL)in the serum of rat in each group were detected;the expression levels of miR-296-3p,interleukin(IL)-6,IL-1 β,tumor necrosis factor(TNF)-α and smooth muscle actin(α-SMA),type Ⅰ collagen(Col1A1),and connective tissue growth factor(CTGF)mRNA in rat liver tissue were detected by qRT-PCR;the expression levels of α-SMA,Col1A1 and CTGF proteins were detected by Western blot.Immunohistochemical staining(IHC)was performed to detect the expression of α-SMA in liver tissue.Target genes of miR-296-3p was predicted by bioinformatic analysis using the online database.Zinc finger and BTB do-main-containing protein20(ZBTB20)mRNA and protein expression levels were detected.Results The pathologi-cal staining results showed that compared with sham group,a large number of infiltrated inflammatory cells and col-lagen deposition were observed in the liver tissues of rats in the BDL group and NC adv group.Compared with NC adv group,the inflammatory cells and collagen deposition decreased in the liver tissues of miR-296-3p adv group.However,in miR-296-3p sponge adv group,collagen product and inflammatory reaction increased.Compared with sham group,the contents of ALT,AST and TBIL in serum of rats in BDL group and NC adv group increased,the expression level of miR-296-3p decreased,the mRNA expression levels of IL-6,IL-1β,TNF-α increased,and the mRNA and protein expression levels of α-SMA,Col1A1 and CTGF increased(all P＜0.05).Compared with the NC adv group,the contents of ALT,AST and TBIL in serum of rats in miR-296-3p adv group decreased,the ex-pression level of miR-296-3p increased,the mRNA expression levels of IL-6,IL-1 β and TNF-α,and the mRNA and protein expression levels of α-SMA,Col1A1 and CTGF in liver tissues decreased(all P＜0.05).The results of miR-296-3p sponge adv group were opposite to those of miR-296-3p adv group(all P＜0.05).The bioinformat-ics website predicted that ZBTB20 might be a candidate target gene of miR-296-3p.Compared with sham group,the expression of ZBTB20 mRNA and protein in the liver tissues of BDL group and NC adv group increased(P＜0.05),and the expression of ZBTB20 in the liver tissues of miR-296-3p adv group decreased compared with NC adv group(P＜0.05).However,the expression of ZBTB20 in liver tissues of miR-296-3p sponge adv group in-creased(P＜0.05).Conclusion miR-296-3p expression decreases in BDL-induced hepatic fibrosis in rats,and miR-296-3p may inhibit hepatic fibrosis in BDL rats by targeting ZBTB20.

Objective To investigate the effect of miR-199a-5p on common bile duct ligation(BDL)-induced liver fibrosis in rats by regulating intestinal flora.Methods The 25 SD rats were randomly divided into five groups:the Sham group,the BDL group,the negative control adenovirus(NC adv)group,the miR-199a-5p adv group and the miR-199a-5p sponge adv group.The pathological changes of liver tissue and the degree of liver fibrosis were ob-served by HE,Masson and Sirius Red staining.The levels of aspartate aminotransferase(AST),alanine amin-otransferase(ALT),total bilirubin(TBIL)and direct bilirubin(DBIL)in serum of rats were determined by a fully automatic biochemical analyzer.The mRNA expression level of miR-199a-5p in liver tissue of rats was detec-ted by qRT-PCR.The protein expression levels of α-smooth muscle actin(α-SMA)and collagen type 1 alpha 1(COL1A1)in liver tissue of rats were detected by double immunofluorescence staining and Western blot experi-ment.Rat feces were collected for 16S rRNA high-throughput sequencing.Results The expression of miR-199a-5p was up-regulated in the liver tissue of BDL rats(P＜0.01).Compared with the NC adv group,the degree of liver injury and collagen deposition were relatively serious,the levels of AST,ALT,TBIL and DBIL in serum and the expression levels of α-SMA and COL1A1 in liver tissue increased in the miR-199a-5p adv group(all P＜0.05).However,the results of miR-199a-5p sponge adv intervention were opposite(all P＜0.05).The 16S rRNA sequencing results showed that rats treated with miR-199a-5p adv were characterized by increased diversity and richness of intestinal microbiota,changed composition of intestinal microbiota,while the results of miR-199a-5p sponge adv interfering with the bacterial community were opposite(all P＜0.05).Conclusion miR-199a-5p promotes liver fibrosis of BDL rats,and its mechanism may be related to regulating the diversity and abundance of intestinal microbiota.

[Objective] To analyze the influencing factors of postoperative patency of longitudinal single suture intussusception microsurgical vasoepididymostomy, to provide reference for improving the repetition rate. [Methods] The clinical data of 82 patients with epididymal obstructive azoospermia who underwent longitudinal single suture intussusception microsurgical vasoepididymostomy in our hospital during Sep.2020 and Jan.2023 were retrospectively analyzed.The postoperative patency and spouse pregnancy were followed up by face to face and / or telephone interview.The effects of age, course of disease, body mass index (BMI), previous medical history (epididymitis, operation history, none), preoperative seminal plasma elastase (SPE) level, anastomosis site, unilateral and bilateral lesion, sperm quality, operation time and hospital stay on the postoperative patency rate were analyzed. [Results] All operations were successful, the follow-up rate was 95.12% (78/82), 78 were married, and the postoperative patency was 78.21% (61/78). Of the 61 patients who achieved patency, 56 were married, and the natural pregnancy rate of spouse was 45.21% (33/73). Univariate analysis showed that patients with age <30 years, course of disease <2 years, preoperative SPE level <290 ng/mL, bilateral anastomosis, body or tail anastomosis and motile sperm had higher postoperative patency rate (P>0.05). BMI, previous history, the number of motile sperms examined by epididymal fluid, the length of operation and hospital stay had no significant effects on postoperative patency (P>0.05). The results of multivariate logistic regression analysis showed that preoperative SPE level (OR=0.998, 95%CI: 0.997-1.000, P=0.008) and (OR=10.724, 95%CI: 2.243-51.283, P=0.003) were significantly correlated with postoperative patency. [Conclusion] The preoperative SPE level and anastomosis site are significant influencing factors of postoperative patency, which is higher in patients with age <30 years, course of disease <2 years, preoperative SPE level <290 ng/mL, bilateral anastomosis, body or tail anastomosis and motile sperm.