Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

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 investigate the protective effect and mechanism of calcium dobesilate on oxidative damage induced by high-glucose in Müller cells.Methods The oxidative damage model of Müller cells induced by high-glucose was established and the cells were divided into 4groups.The control group was cultured normally,and the high glucose group was cultured in the medium of 35mmol/L glucose.The control+calcium dobesilate group was treated with 0.5μmol/L calcium dobesilate intervention cells on the basis of routine culture,and the high sugar+calcium dobesilate group was treated with 0.5μmol/L calcium dobesilate intervention cells on the basis of high glucose.Cell proliferation was assessed by CCK-8,apoptosis was detected by flow cytometry,and oxidative stress markers were detected by the kit.Intracellular correction potassium channel subtype 4.1(Kir4.1)and aquaporin 4(AQP4)protein levels were detected by western blot.Results Compared with the control group,the proliferative activity of Müller cells of the high glucose group was decreased,apoptosis rate was increased,oxidative stress occurred,AQP4 protein expression level was increased and Kir4.1 protein level was decreased(P＜0.05).Compared with the high glucose group,the cell activity and apoptosis rate of the high glucose+calcium do-besilate group were increased,the oxidative stress damage was alleviated,the AQP4 protein expression level was decreased and the Kir4.1 protein level was increased(P＜0.05).Conclusion Calcium dobesilate may inhibit the oxidative damage of Müller cells induced by high-glucose by regulating the AQP4/Kir4.1 axis.

Objective:To observe the effect of point injection at Zusanli(ST36)plus abdominal point application on gastrointestinal dysfunction after laparoscopic surgery.Methods:A total of 204 patients with gastrointestinal dysfunction after laparoscopic surgery were recruited and divided into four groups using the random number table method,with 51 cases in each group.The control group received conventional postoperative intervention.In addition to the treatment in the control group,the point injection group was given point injection at Zusanli(ST36),the application group was offered abdominal point application,and the integrated group received point injection at Zusanli(ST36)and abdominal point application.The treatment lasted 3 consecutive days in all four groups.The recovery time of gastrointestinal function indicators and the incidence rate of postoperative nausea and vomiting(PONV)were observed and recorded.Before and after treatment,the visual analog scale(VAS)was used to assess abdominal pain intensity,the venous blood type 1 helper T cells/type 2 helper T cells(Th1/Th2)was determined,the serum levels of interleukin(IL)-6 and interferon(IFN)-γ were detected using the enzyme-linked immunosorbent assay,and the plasma levels of motilin and gastrin were measured using radioimmunoassay.Results:Compared to the control group,the first exhaust time,the first defecation time,and the time of restoring fluid diet came earlier in the other three groups(P<0.05)and were earlier in the integrated group than in the point injection and application groups(P<0.05).The point injection,application,and integrated groups had a lower PONV incidence rate than the control group,and the integrated group was lower than the point injection and application groups(P<0.05).The intra-group comparisons showed that the VAS score and the levels of IL-6 and INF-γ decreased after treatment in all four groups(P<0.05);the point injection,application,and integrated groups were lower than the control group(P<0.05),and the integrated group was lower than the point injection and application groups(P<0.05).The intra-group comparisons also demonstrated that the levels of Th1/Th2,motilin,and gastrin increased after the intervention in the four groups(P<0.05);the point injection,application,and integrated groups were higher than the control group(P<0.05),and the integrated group was higher than the point injection and application groups(P<0.05).Conclusion:Point injection at Zusanli(ST36)plus abdominal point application can encourage postoperative exhaust,defecation,and the recovery of diet fluid,alleviate postoperative abdominal pain,reduce PONV,balance Th1/Th2,and regulate the secretion of motilin and gastrin in patients with gastrointestinal dysfunction after laparoscopic surgery.

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 investigate the protective effect and mechanism of calcium dobesilate on oxidative damage induced by high-glucose in Müller cells.Methods The oxidative damage model of Müller cells induced by high-glucose was established and the cells were divided into 4groups.The control group was cultured normally,and the high glucose group was cultured in the medium of 35mmol/L glucose.The control+calcium dobesilate group was treated with 0.5μmol/L calcium dobesilate intervention cells on the basis of routine culture,and the high sugar+calcium dobesilate group was treated with 0.5μmol/L calcium dobesilate intervention cells on the basis of high glucose.Cell proliferation was assessed by CCK-8,apoptosis was detected by flow cytometry,and oxidative stress markers were detected by the kit.Intracellular correction potassium channel subtype 4.1(Kir4.1)and aquaporin 4(AQP4)protein levels were detected by western blot.Results Compared with the control group,the proliferative activity of Müller cells of the high glucose group was decreased,apoptosis rate was increased,oxidative stress occurred,AQP4 protein expression level was increased and Kir4.1 protein level was decreased(P＜0.05).Compared with the high glucose group,the cell activity and apoptosis rate of the high glucose+calcium do-besilate group were increased,the oxidative stress damage was alleviated,the AQP4 protein expression level was decreased and the Kir4.1 protein level was increased(P＜0.05).Conclusion Calcium dobesilate may inhibit the oxidative damage of Müller cells induced by high-glucose by regulating the AQP4/Kir4.1 axis.

Objective To investigate the protective effect of LncRNA MEG3 on the retina in early-stage diabetic rats through regulation of the COX-2/PGE2/VEGF signaling pathway.Methods 50 male SD rats of SPF grade were selected for the study.Among them,10 rats were assigned to the control group,while 40 rats were used to establish diabetic retinopathy models.A total of 32 rats successfully underwent modeling and were subsequently divided into four groups(n=8 per group):model group,negative control group,MEG3 overexpression group,and MEG3 overexpression+COX-2 inhibitor group.Histopathological changes,vascular permeability,glucose and lipid metabolism,inflammatory factors,oxidative stress indices,PGE2 levels,as well as the relative mRNA and protein expression levels of COX-2 and VEGF were evaluated in each group.Results Compared with the control group,HDL-C,CAT,GSH-PX,and SOD levels were significantly decreased,whereas the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were significantly increased in the model group(P<0.05).Compared with the negative control group,HDL-C,CAT,GSH-PX,and SOD levels were significantly increased in the MEG3 overexpression group,while the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were significantly decreased(P<0.05).Compared with the MEG3 overexpression group,HDL-C,CAT,GSH-PX,and SOD levels were further increased in the MEG3 overexpression+COX-2 inhibitor group,and the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were further decreased(P<0.05).Conclusion LncRNA MEG3 is capable of regulating the COX-2/PGE2/VEGF pathway,enhancing glucose and lipid metabolism in rats,suppressing the expression of inflammatory factors,attenuating stress responses,and alleviating diabetic retinopathy.

Objective To investigate the protective effect of LncRNA MEG3 on the retina in early-stage diabetic rats through regulation of the COX-2/PGE2/VEGF signaling pathway.Methods 50 male SD rats of SPF grade were selected for the study.Among them,10 rats were assigned to the control group,while 40 rats were used to establish diabetic retinopathy models.A total of 32 rats successfully underwent modeling and were subsequently divided into four groups(n=8 per group):model group,negative control group,MEG3 overexpression group,and MEG3 overexpression+COX-2 inhibitor group.Histopathological changes,vascular permeability,glucose and lipid metabolism,inflammatory factors,oxidative stress indices,PGE2 levels,as well as the relative mRNA and protein expression levels of COX-2 and VEGF were evaluated in each group.Results Compared with the control group,HDL-C,CAT,GSH-PX,and SOD levels were significantly decreased,whereas the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were significantly increased in the model group(P<0.05).Compared with the negative control group,HDL-C,CAT,GSH-PX,and SOD levels were significantly increased in the MEG3 overexpression group,while the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were significantly decreased(P<0.05).Compared with the MEG3 overexpression group,HDL-C,CAT,GSH-PX,and SOD levels were further increased in the MEG3 overexpression+COX-2 inhibitor group,and the mRNA and protein expression levels of vascular permeability,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,MDA,PGE2,COX-2,and VEGF were further decreased(P<0.05).Conclusion LncRNA MEG3 is capable of regulating the COX-2/PGE2/VEGF pathway,enhancing glucose and lipid metabolism in rats,suppressing the expression of inflammatory factors,attenuating stress responses,and alleviating diabetic retinopathy.

Objective:To observe the effect of point injection at Zusanli(ST36)plus abdominal point application on gastrointestinal dysfunction after laparoscopic surgery.Methods:A total of 204 patients with gastrointestinal dysfunction after laparoscopic surgery were recruited and divided into four groups using the random number table method,with 51 cases in each group.The control group received conventional postoperative intervention.In addition to the treatment in the control group,the point injection group was given point injection at Zusanli(ST36),the application group was offered abdominal point application,and the integrated group received point injection at Zusanli(ST36)and abdominal point application.The treatment lasted 3 consecutive days in all four groups.The recovery time of gastrointestinal function indicators and the incidence rate of postoperative nausea and vomiting(PONV)were observed and recorded.Before and after treatment,the visual analog scale(VAS)was used to assess abdominal pain intensity,the venous blood type 1 helper T cells/type 2 helper T cells(Th1/Th2)was determined,the serum levels of interleukin(IL)-6 and interferon(IFN)-γ were detected using the enzyme-linked immunosorbent assay,and the plasma levels of motilin and gastrin were measured using radioimmunoassay.Results:Compared to the control group,the first exhaust time,the first defecation time,and the time of restoring fluid diet came earlier in the other three groups(P<0.05)and were earlier in the integrated group than in the point injection and application groups(P<0.05).The point injection,application,and integrated groups had a lower PONV incidence rate than the control group,and the integrated group was lower than the point injection and application groups(P<0.05).The intra-group comparisons showed that the VAS score and the levels of IL-6 and INF-γ decreased after treatment in all four groups(P<0.05);the point injection,application,and integrated groups were lower than the control group(P<0.05),and the integrated group was lower than the point injection and application groups(P<0.05).The intra-group comparisons also demonstrated that the levels of Th1/Th2,motilin,and gastrin increased after the intervention in the four groups(P<0.05);the point injection,application,and integrated groups were higher than the control group(P<0.05),and the integrated group was higher than the point injection and application groups(P<0.05).Conclusion:Point injection at Zusanli(ST36)plus abdominal point application can encourage postoperative exhaust,defecation,and the recovery of diet fluid,alleviate postoperative abdominal pain,reduce PONV,balance Th1/Th2,and regulate the secretion of motilin and gastrin in patients with gastrointestinal dysfunction after laparoscopic surgery.

Background Hexavalent chromium [Cr(VI)] exposure can cause structural disruption of intestinal flora and functional impairment. Vitamin C (VC) is one of the essential micronutrients, which plays an important role in promoting the growth of intestinal probiotics, improving the intestinal barrier, and maintaining the homeostasis of intestinal flora. However, the regulatory effect of VC on the intestinal flora disorders caused by Cr(VI) exposure remains to be investigated. Objective To investigate the effect of VC on intestinal flora disruption in mice due to Cr(VI) exposure. Methods Thirty-two SPF-grade C57BL/6 mice were acclimatized and fed for 3 d and randomly divided into control (Con), VC, potassium dichromate [K₂Cr₂O₇, Cr(VI)], and VC+K₂Cr₂O₇ [VC+Cr(VI)] groups. At 8:00 a.m. on day 4, the Con group (double-distilled water given by gavage and injected intraperitoneally), the VC group (VC given by gavage and double-distilled water injected intraperitoneally), the Cr(VI) group (double-distilled water given by gavage and K₂Cr₂O₇ solution injected intraperitoneally), and the VC+Cr(VI) group (VC given by gavage and K₂Cr₂O₇ solution injected intraperitoneally) were treated. The dose of VC was 200 mg·kg⁻¹, and the dose of K₂Cr₂O₇ was 1.25 mg·kg⁻¹. The mice were treated for 45 consecutive days and then executed, the contents of the colon were sampled in sterile freezing tubes, and three replicates were collected from each group. After labeling, the samples were immediately put into liquid nitrogen for rapid freezing. After all the samples were collected, they were transferred to a -80 ℃ ultra-low temperature refrigerator for storage. Samples of colon contents were analyzed for intestinal flora structure by high-throughput sequencing and bioinformatics software. Results The Cr(VI) exposure resulted in reduced body weight gain values in mice compared to the Con group. Pathological changes occurred in the ileal tissue of mice, with significant inflammatory cell infiltration in the Cr(VI) group and reduced inflammatory cell infiltration in the VC+Cr(VI) group. The number of operational taxonomic units (OTUs) of intestinal flora was altered in the Cr(VI) group of mice. In the α diversity analysis, the mean Sobs index in the Cr(VI) group was 240.333±67.796, the Chao index was 258.173±64.813, and the Ace index was 259.481±66.891, which were significantly lower than those in the Con group (P<0.05), the PD whole tree index in the Cr(VI) group was 27.863±2.399, which was significantly higher than that in the Con group (P<0.05), and the VC intervention significantly reversed the changes of the above indexes due to Cr(VI) exposure (P<0.05). In the β diversity analysis, the principal coordinates analysis (PCoA) results showed a significant separation between the Cr(VI) group and the Con group, and after the VC intervention, there was a retraction of the separation trend and the difference was reduced. The multi-sample similarity dendrogram results showed that the control and the VC groups clustered together first, then with the VC+Cr(VI) group, and finally with the Cr(VI) group. The abundances of Bacteroidetes, Saccharibacteria, and Tenericutes in the intestine of mice in the Cr(VI) group were decreased, and the abundance of Firmicutes was increased; the abundances of Lactobacillus, Alistipes, Bacteroides, and Ruminiclostridium were also increased. Included among these, Bacteroides showed a significantly higher abundance compared to the control mice (P<0.05). Changes in the abundances of phyla and genera of the above mentioned gut microorganisms were reversed after the VC intervention. Conclusion Cr(VI) exposure can lead to intestinal damage and disorganization of the intestinal flora structure in mice, while VC intervention can ameliorate the above changes to a certain extent and normalize the intestinal flora structure.