ObjectiveTo explore the effect and mechanism of Taishan Panshi powder （TSPSP） on inhibiting oxidative stress injury in human chorionic trophoblast cells （HTR-8/SVneo）， and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion （SA）. MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus （GEO） database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP， and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments， HTR-8/SVneo cells were divided into blank group， model group， TSPSP-containing serum 2.5%， 5%， 10% groups， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group （ML385， 30 μmol·L^-1）. Except for the blank group， other groups were stimulated with 150 μmol·L^-1 H₂O₂ for 3 h to establish a cell oxidative stress injury model. After successful modeling， the blank group and model group were given 10% blank serum， each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum， and the Nrf2 inhibitor group was additionally given 30 μmol·L^-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h， and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde （MDA）， Fe²⁺， and Glutathione （GSH） were detected by enzyme-linked immunosorbent assay （ELISA）. Intracellular reactive oxygen species （ROS） level was detected by a fluorescent probe （DCF-DA）. The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 （KEAP1）， Nrf2， and forkhead box protein O3 （FoxO3） in cells were detected by immunofluorescence （IF） and real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of KEAP1， Nrf2， FoxO3， Glutathione peroxidase 4 （GPX4）， and superoxide dismutase （SOD） in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1， Nrf2， and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway， nine significantly differential pathways were identified （P<0.05）， among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology， and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response， FOXO and MAPK signaling pathways， etc. In in vitro experiments， compared with the blank group， the cell viability in the model group was significantly decreased （P<0.01）. Compared with the model group， the cell viability in each TSPSP-containing serum group was significantly increased （P<0.01）. Compared with the 10% TSPSP-containing serum group， the cell viability in the ML385 group decreased to approximately 70% （P<0.01）. Compared with the blank group， the model group showed significantly increased contents of MDA， Fe²⁺， and ROS， decreased GSH expression （P<0.01）， significantly reduced cell migration rate （P<0.01）， and increased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.01）， while decreased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.01）. Compared with the model group， each TSPSP-containing serum group showed significantly decreased contents of MDA， Fe²⁺， and ROS， increased GSH expression （P<0.01）， significantly increased migration rate （P<0.01）， significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.05， P<0.01）， and significantly increased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.05， P<0.01）. Compared with the 10% TSPSP-containing serum group， the ML385 group showed reversed trends in all indicators （P<0.05， P<0.01）. ConclusionTSPSP can inhibit H₂O₂-induced oxidative stress injury of trophoblast cells， and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.

ObjectiveTo explore the effect and mechanism of Taishan Panshi powder （TSPSP） on inhibiting oxidative stress injury in human chorionic trophoblast cells （HTR-8/SVneo）， and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion （SA）. MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus （GEO） database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP， and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments， HTR-8/SVneo cells were divided into blank group， model group， TSPSP-containing serum 2.5%， 5%， 10% groups， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group （ML385， 30 μmol·L^-1）. Except for the blank group， other groups were stimulated with 150 μmol·L^-1 H₂O₂ for 3 h to establish a cell oxidative stress injury model. After successful modeling， the blank group and model group were given 10% blank serum， each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum， and the Nrf2 inhibitor group was additionally given 30 μmol·L^-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h， and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde （MDA）， Fe²⁺， and Glutathione （GSH） were detected by enzyme-linked immunosorbent assay （ELISA）. Intracellular reactive oxygen species （ROS） level was detected by a fluorescent probe （DCF-DA）. The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 （KEAP1）， Nrf2， and forkhead box protein O3 （FoxO3） in cells were detected by immunofluorescence （IF） and real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of KEAP1， Nrf2， FoxO3， Glutathione peroxidase 4 （GPX4）， and superoxide dismutase （SOD） in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1， Nrf2， and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway， nine significantly differential pathways were identified （P<0.05）， among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology， and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response， FOXO and MAPK signaling pathways， etc. In in vitro experiments， compared with the blank group， the cell viability in the model group was significantly decreased （P<0.01）. Compared with the model group， the cell viability in each TSPSP-containing serum group was significantly increased （P<0.01）. Compared with the 10% TSPSP-containing serum group， the cell viability in the ML385 group decreased to approximately 70% （P<0.01）. Compared with the blank group， the model group showed significantly increased contents of MDA， Fe²⁺， and ROS， decreased GSH expression （P<0.01）， significantly reduced cell migration rate （P<0.01）， and increased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.01）， while decreased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.01）. Compared with the model group， each TSPSP-containing serum group showed significantly decreased contents of MDA， Fe²⁺， and ROS， increased GSH expression （P<0.01）， significantly increased migration rate （P<0.01）， significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 （P<0.05， P<0.01）， and significantly increased protein and mRNA expression levels of Nrf2， GPX4， and SOD （P<0.05， P<0.01）. Compared with the 10% TSPSP-containing serum group， the ML385 group showed reversed trends in all indicators （P<0.05， P<0.01）. ConclusionTSPSP can inhibit H₂O₂-induced oxidative stress injury of trophoblast cells， and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.

The histological assessment has been considered as a detailed and accurate method for measuring the disease activity in inflammatory bowel disease(IBD).In ulcerative colitis(UC),histological activity has been demon-strated to be associated with a higher rate of relapse,prolonged corticosteroid use and long-term complications,even in patients who have achieved endoscopic remission.Therefore,histological remission may be regarded as a potential ther-apeutic target.This article introduces the clinical significance of disease activity assessment in IBD,focusing on the re-view of validated and newly proposed histological scoring systems for IBD,and explores the priorities for future research needs.

Objective To analyze the differences of brain activity between first-episode untreated depressive patients with and without suicidal ideation(SI),and its correlations with clinical characteristics.Methods A total of 40 major depressive disorder(MDD)patients with SI(MDD+SI group),40 patients without SI MDD(MDD+NSI group),and 40 healthy controls(HC)(HC group)were enrolled.The 17-item Hamilton depression scale(HAMD-17)and Beck scale for suicide ideation(BSI)were used to assess the severity of depression and SI,respectively.MRI data were collected.The values of fractional amplitude of low-frequency fluctuation(fALFF)were calculated.Results(1)Compared with the HC group,the MDD+NSI group showed decreases in the fALFF val-ues of the default network and attention network.The fALFF values of the attention network in the MDD+SI group showed decreases.Compared with the MDD+NSI group,the MDD+SI group showed decreases in the fALFF values of the attention network.(2)The fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.55;P<0.001)in the MDD+NSI group,while the fALFF values in the left middle frontal gyrus were negatively correlated with the total score of HAMD-17(r=-0.53;P<0.001)and the total score of BSI(r=-0.51;P<0.001)in the MDD+SI group.(3)The optimal critical value of fALFF value in left middle frontal gyrus for predicting SI occurrence in MDD patients was-0.039,area under the curve(AUC)was 0.76,sensitivity was 0.63,and specificity was 0.80.Conclusion The decreased local activity intensity in the left middle frontal gyrus of the brain might be the central mechanism for the occurrence of SI in MDD patients.In addition,the left middle frontal gyrus might have certain value in identifying SI and predicting the severity of SI.

Objective:To summarize the initial experience of 5G-ultra-long-distance robotic hepatectomy.Methods:This is a retrospective case series study. The clinical information from 5 cases of 5G ultra-long-distance robot-assisted hepatectomy performed was collected from June 2023 to October 2024, in collaboration between Sir Run Run Shaw Hospital, Zhejiang University School of Medicine in Hangzhou and Alaer Hospital, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine in Alaer, located 4 600 km apart. The patients comprised 1 male and 4 females, aged from 36 to 59 years, with an average age of 48 years. Their body mass index ranged from 20.4 to 30.9 kg/m2, with an average of 24.62 kg/m2. Preoperatively, 5 patients were diagnosed with liver disease requiring hepatectomy. The operations used 5G ultra-remote four-arm endoscopic robot surgery system. The remote control room was located in Sir Run Run Shaw Hospital (Hangzhou, Zhejiang), and the robot operating room was located in Alaer Hospital (Alaer, Xinjiang). The wired network relied on 60 Mb/s high-speed public Internet special line (China Telecom). In order to ensure the security of data transmission, the system implemented a double-layer encryption strategy for the wired network, and carried out strict debugging and verification for both the wired and wireless networks. Perioperative data and information on network performance were collected for 5 patients.Results:The surgical duration of the 5 cases of 5G ultra-long-distance robot-assisted hepatectomy ranged from 49 to 342 minutes, with an average of 184 minutes. Intraoperative blood loss varied from 5 to 800 ml, averaging 183 ml. Network performance was evaluated during the surgery, revealing an average network latency of 108.2 ms, with no significant lag or delay observed during any of the procedures. All patients recovered smoothly, with a postoperative hospital stay ranging from 5 to 10 days, averaging 7.2 days. Postoperative complications included 1 case of hypoproteinemia and 1 case of pleural effusion. Pathological examination confirmed that all cases suffered benign liver diseases (three patients with hepatic hemangioma, one with regenerative nodule in cirrhosis, and one with hepatolithiasis and choledocholithiasis).Conclusion:The preliminary exploration of clinical practice indicated that 5G-ultra-long-distance robot-assisted surgery is feasible for hepatectomy, with no severe complications affecting patients′ recovery.

Objective:To investigate the relationship between the expression of microtubule-associated protein light chain 3B (LC3B), Beclin-1, and p62 in serum CD 4+ T lymphocytes of patients infected with varicella-zoster virus (VZV) and viral replication. Methods:This study used a cross-sectional design. A total of 106 patients with VZV who received treatment at The First People's Hospital of Huzhou between October 2018 and October 2019 were included in the study group. Additionally, 50 healthy individuals who underwent health examinations during the same period were included in the control group. The expression levels of LC3B, Beclin-1, and p62 in serum CD 4+ T lymphocytes among patients with different VZV DNA copy numbers were compared. The effects of different levels of LC3B, Beclin-1, and p62 on disease severity were evaluated. Spearman correlation analysis was performed to investigate the relationship between the expression of LC3B, Beclin-1, and p62 in the peripheral blood CD 4+ T lymphocytes of VZV-infected patients, viral replication, and disease duration. Results:The relative expression levels of LC3B and Beclin-1 in peripheral blood CD 4+ T lymphocytes of the study group were (60.19 ± 7.59)% and (34.99 ± 4.34)%, respectively, which were significantly higher than those in the control group [(37.71 ± 4.33)%, (16.18 ± 1.92)%, t = 19.48, 29.29, both P < 0.001]. The relative expression level of p62 in the study group was significantly lower than that in the control group [(5.81 ± 0.58)% vs. (10.11 ± 1.24)%, t = -29.57, P < 0.001]. The peripheral blood VZV DNA copy number in the study group was (4.28 ± 0.47). In patients with a VZV DNA copy number ≥ 4.28, the expression levels of LC3B [(72.22 ± 8.83)%] and Beclin-1 [(40.09 ± 5.56)%] were significantly higher than those in patients with a VZV DNA copy number < 4.28 [LC3B: (51.23 ± 6.88)%, Beclin-1: (29.67 ± 3.12)%, t = 13.57, 11.77, both P < 0.001]. The expression level of p62 in patients with a VZV DNA copy number ≥ 4.28 [(4.77 ± 0.36)%] was significantly lower than that in patients with a VZV DNA copy number < 4.28 [(6.98 ± 0.79) %, t = -18.76, P < 0.001]. The expression levels of LC3B and Beclin-1 in patients at moderate or advanced stages were significantly higher than those in patients with early-stage VZV ( P < 0.05), while the expression levels of p62 in patients with moderate- or advanced-stage VZV were significantly lower than those in patients with early-stage VZV (both P < 0.05). Additionally, the expression levels of LC3B and Beclin-1 were positively correlated with viral replication ( r = 0.817, 0.839) and disease duration ( r = 0.849, 0.822, all P < 0.001). The expression level of p62 was negatively correlated with viral replication and disease duration ( r = -0.850, -0.822, both P < 0.001). Conclusions:In patients infected with VZV, the autophagy levels in peripheral blood CD 4+ T lymphocytes were significantly upregulated, as evidenced by increased expression of LC3B and Beclin-1 and decreased expression of p62. Autophagy positively influences viral replication, with elevated autophagy levels promoting viral replication.

OBJCTIVE To evaluate the therapeutic efficacy of intranasal administration of pirfeni-done in treating paraquat-induced pulmonary fibrosis in mice across treatment durations.METHODS Eight-week-old male C57BL/6 mice were randomly divided into six groups(n=8 per group):the normal control group(saline),pirfenidone control group,paraquat group,and three treatment groups receiving a combination of paraquat and pirfenidone for 15,10 and 5 d,respectively.Except the normal and pirfeni-done control groups,all the mice received intraperitoneal injection of paraquat(35 mg·kg-1)to induce pulmonary fibrosis.In the treatment groups,pirfenidone(20 mg·kg-1)was delivered intranasally once daily,beginning on days 1,6,and 11 post-paraquat exposure,until day 15.Fifteen days after paraquat exposure,pulmonary function tests,micro-CT imaging,and arterial blood gas analysis were performed.Histopathological changes and collagen fiber deposition in lung tissues were examined using HE and Masson staining respectively.The protein expression levels of fibrosis markers,including fibronectin(FN),collagen typeⅠ(CollⅠ),E-cadherin(E-cad),vimentin(Vim),and α-smooth muscle actin(α-SMA),were detected by Western blotting.Additionally,inflammatory and pro-fibrotic cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-8,IL-1β,and connective tissue growth factor(CTGF),were quantified using ELISA.RESULTS Compared with the normal control group,mice treated with paraquat exhibited significant respiratory alterations,including prolonged expiratory time(TE),increased enhanced pause(PENH),and reduced tidal volume(TV).CT imaging revealed reticular high-density shadows and ground-glass opacities in paraquat-treated mice.Blood gas analysis showed reduced partial pressure of oxygen(PaO2),oxygen saturation of blood(SaO2),fractional oxygen saturation of hemoglobin(FO2 Hb),and central venous oxygen saturation(ScvO2),along with increased partial pressure of carbon dioxide(PaCO2)and fractional deoxyhemoglobin saturation(FHHb),indicating that mice exposed to para-quat exhibited severe hypoxemia and hypercapnia.Histological evaluation highlighted pronounced lung interstitial thickening,alveolar collapse,inflammatory infiltration,and extensive fibrotic changes marked by collagen accumulation.Furthermore,exposure to paraquat significantly increased the protein levels of FN,CollⅠ,vimentin,and α-SMA,markedly reduced E-cadherin levels and elevated the levels of inflam-matory cytokines(TNF-α,IL-6,IL-8 and IL-1β)as well as the pro-fibrotic cytokine CTGF.Pirfenidone treat-ment demonstrated time-dependent efficacy,with the 15 d group showing the most significant improvements in pulmonary function as evidenced by reduced PENH levels and increased TV,EV and MV.CT imaging revealed a decrease in high-density opacities and improved lung transparency after pirfenidone treatment.In addition,arterial blood gas measurements indicated markedly elevated levels of PaO2,SaO2 and FO2 Hb.Histological analysis showed that pirfenidone alleviated lung interstitial thick-ening,reduced inflammatory cell infiltration,and decreased collagen deposition.At the molecular level,pirfenidone significantly reduced the protein expressions of FN,CollⅠ,Vim and α-SMA,while increasing E-cad levels.Furthermore,inflammatory cytokines,particularly IL-6 and IL-1β,were notably suppressed following pirfenidone intervention.CONCLUSION Intranasal administration of pirfenidone can exhibit potent time-dependent anti-fibrotic efficacy in paraquat-induced pulmonary fibrosis,with early interven-tions delivering the most substantial therapeutic benefits.

Objective:To investigate the relationship between the expression of microtubule-associated protein light chain 3B (LC3B), Beclin-1, and p62 in serum CD 4+ T lymphocytes of patients infected with varicella-zoster virus (VZV) and viral replication. Methods:This study used a cross-sectional design. A total of 106 patients with VZV who received treatment at The First People's Hospital of Huzhou between October 2018 and October 2019 were included in the study group. Additionally, 50 healthy individuals who underwent health examinations during the same period were included in the control group. The expression levels of LC3B, Beclin-1, and p62 in serum CD 4+ T lymphocytes among patients with different VZV DNA copy numbers were compared. The effects of different levels of LC3B, Beclin-1, and p62 on disease severity were evaluated. Spearman correlation analysis was performed to investigate the relationship between the expression of LC3B, Beclin-1, and p62 in the peripheral blood CD 4+ T lymphocytes of VZV-infected patients, viral replication, and disease duration. Results:The relative expression levels of LC3B and Beclin-1 in peripheral blood CD 4+ T lymphocytes of the study group were (60.19 ± 7.59)% and (34.99 ± 4.34)%, respectively, which were significantly higher than those in the control group [(37.71 ± 4.33)%, (16.18 ± 1.92)%, t = 19.48, 29.29, both P < 0.001]. The relative expression level of p62 in the study group was significantly lower than that in the control group [(5.81 ± 0.58)% vs. (10.11 ± 1.24)%, t = -29.57, P < 0.001]. The peripheral blood VZV DNA copy number in the study group was (4.28 ± 0.47). In patients with a VZV DNA copy number ≥ 4.28, the expression levels of LC3B [(72.22 ± 8.83)%] and Beclin-1 [(40.09 ± 5.56)%] were significantly higher than those in patients with a VZV DNA copy number < 4.28 [LC3B: (51.23 ± 6.88)%, Beclin-1: (29.67 ± 3.12)%, t = 13.57, 11.77, both P < 0.001]. The expression level of p62 in patients with a VZV DNA copy number ≥ 4.28 [(4.77 ± 0.36)%] was significantly lower than that in patients with a VZV DNA copy number < 4.28 [(6.98 ± 0.79) %, t = -18.76, P < 0.001]. The expression levels of LC3B and Beclin-1 in patients at moderate or advanced stages were significantly higher than those in patients with early-stage VZV ( P < 0.05), while the expression levels of p62 in patients with moderate- or advanced-stage VZV were significantly lower than those in patients with early-stage VZV (both P < 0.05). Additionally, the expression levels of LC3B and Beclin-1 were positively correlated with viral replication ( r = 0.817, 0.839) and disease duration ( r = 0.849, 0.822, all P < 0.001). The expression level of p62 was negatively correlated with viral replication and disease duration ( r = -0.850, -0.822, both P < 0.001). Conclusions:In patients infected with VZV, the autophagy levels in peripheral blood CD 4+ T lymphocytes were significantly upregulated, as evidenced by increased expression of LC3B and Beclin-1 and decreased expression of p62. Autophagy positively influences viral replication, with elevated autophagy levels promoting viral replication.

OBJCTIVE To evaluate the therapeutic efficacy of intranasal administration of pirfeni-done in treating paraquat-induced pulmonary fibrosis in mice across treatment durations.METHODS Eight-week-old male C57BL/6 mice were randomly divided into six groups(n=8 per group):the normal control group(saline),pirfenidone control group,paraquat group,and three treatment groups receiving a combination of paraquat and pirfenidone for 15,10 and 5 d,respectively.Except the normal and pirfeni-done control groups,all the mice received intraperitoneal injection of paraquat(35 mg·kg-1)to induce pulmonary fibrosis.In the treatment groups,pirfenidone(20 mg·kg-1)was delivered intranasally once daily,beginning on days 1,6,and 11 post-paraquat exposure,until day 15.Fifteen days after paraquat exposure,pulmonary function tests,micro-CT imaging,and arterial blood gas analysis were performed.Histopathological changes and collagen fiber deposition in lung tissues were examined using HE and Masson staining respectively.The protein expression levels of fibrosis markers,including fibronectin(FN),collagen typeⅠ(CollⅠ),E-cadherin(E-cad),vimentin(Vim),and α-smooth muscle actin(α-SMA),were detected by Western blotting.Additionally,inflammatory and pro-fibrotic cytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-8,IL-1β,and connective tissue growth factor(CTGF),were quantified using ELISA.RESULTS Compared with the normal control group,mice treated with paraquat exhibited significant respiratory alterations,including prolonged expiratory time(TE),increased enhanced pause(PENH),and reduced tidal volume(TV).CT imaging revealed reticular high-density shadows and ground-glass opacities in paraquat-treated mice.Blood gas analysis showed reduced partial pressure of oxygen(PaO2),oxygen saturation of blood(SaO2),fractional oxygen saturation of hemoglobin(FO2 Hb),and central venous oxygen saturation(ScvO2),along with increased partial pressure of carbon dioxide(PaCO2)and fractional deoxyhemoglobin saturation(FHHb),indicating that mice exposed to para-quat exhibited severe hypoxemia and hypercapnia.Histological evaluation highlighted pronounced lung interstitial thickening,alveolar collapse,inflammatory infiltration,and extensive fibrotic changes marked by collagen accumulation.Furthermore,exposure to paraquat significantly increased the protein levels of FN,CollⅠ,vimentin,and α-SMA,markedly reduced E-cadherin levels and elevated the levels of inflam-matory cytokines(TNF-α,IL-6,IL-8 and IL-1β)as well as the pro-fibrotic cytokine CTGF.Pirfenidone treat-ment demonstrated time-dependent efficacy,with the 15 d group showing the most significant improvements in pulmonary function as evidenced by reduced PENH levels and increased TV,EV and MV.CT imaging revealed a decrease in high-density opacities and improved lung transparency after pirfenidone treatment.In addition,arterial blood gas measurements indicated markedly elevated levels of PaO2,SaO2 and FO2 Hb.Histological analysis showed that pirfenidone alleviated lung interstitial thick-ening,reduced inflammatory cell infiltration,and decreased collagen deposition.At the molecular level,pirfenidone significantly reduced the protein expressions of FN,CollⅠ,Vim and α-SMA,while increasing E-cad levels.Furthermore,inflammatory cytokines,particularly IL-6 and IL-1β,were notably suppressed following pirfenidone intervention.CONCLUSION Intranasal administration of pirfenidone can exhibit potent time-dependent anti-fibrotic efficacy in paraquat-induced pulmonary fibrosis,with early interven-tions delivering the most substantial therapeutic benefits.

The histological assessment has been considered as a detailed and accurate method for measuring the disease activity in inflammatory bowel disease(IBD).In ulcerative colitis(UC),histological activity has been demon-strated to be associated with a higher rate of relapse,prolonged corticosteroid use and long-term complications,even in patients who have achieved endoscopic remission.Therefore,histological remission may be regarded as a potential ther-apeutic target.This article introduces the clinical significance of disease activity assessment in IBD,focusing on the re-view of validated and newly proposed histological scoring systems for IBD,and explores the priorities for future research needs.