Objective To investigate the role and underlying mechanisms of oxoglutarate dehydrogenase-L(OGDHL)in renal fibrosis.Methods Twelve male wild-type C57BL/6J mice(8 weeks old,weighting about 25 g)were randomly divided into control group and model group(n=6).A mouse model of renal fibrosis was established by unilateral ureteral obstruction(UUO).HE staining,immunofluorescence assay,and immunohistochemical and Masson staining were applied to assess the extent of renal fibrosis.Human kidney-2 proximal tubule cell line(HK-2)were randomly divided into blank plasmid group(Vector),OGDHL overexpression group(OGDHL OE),blank plasmid+TGF-β1 treatment group(TGF-β1+Vector),TGF-β1 treatment and OGDHL overexpression group(TGF-β1+OGDHL OE).Transmission electron microscopy(TEM)was employed to observe mitochondrial morphology.RT-qPCR,Western blotting and immunofluorescence assay were used to detect the expression levels of OGDHL and mitochondrial metabolism-related genes.Adenosine triphosphate(ATP)level,oxygen consumption rate(OCR),extracellular acidification rate(ECAR)and other mitochondrial metabolism-related indicators were detected with corresponding reagent kits and Agilent Seahorse.Results UUO operation resulted in obvious thinning of the renal cortex,significant hydronephrosis.HE staining revealed that tubular atrophy accompanied by dilated tubular lumens in the kidneys.Immunofluorescence,immunohistochemical and Masson staining showed obvious renal fibrosis after UUO operation.In the mouse model of renal fibrosis,the expression of OGDHL was decreased by 82.9%at mRNA level(P<0.001)and 81.9%at protein level(P<0.001),the production of mitochondrial ATP was reduced by 0.970±0.151 μmol/L(P<0.01),and notable damaged mitochondrial structure was observed,with maximum breathing capacity decreased by 25.260±1.920 pmol/min(P<0.001),expression levels of fatty acid oxidation-related genes were declined by 50.2%(P<0.05),while glycolysis was enhanced,with the genes related to glycolysis increased by 2.5 times when compared with those in the control group(P<0.05).After OGDHL overexpression,mitochondrial morphological damage was significantly improved,ATP production was increased by 0.980±0.090 μmol/L(P<0.05),with significantly alleviated energy metabolism disorder and renal fibrosis(P<0.05).Conclusion OGDHL regulates mitochondrial metabolic reprogramming of renal tubular epithelial cells to alleviate fibrosis,suggesting that OGDHL may be a new therapeutic target for renal fibrosis.

OBJECTIVE To investigate the role and mechanisms of the soluble guanylate cyclase(sGC)stimulator sGC003 in improving high altitude pulmonary edema(HAPE)in mice.METHODS Mice were randomly assigned to a normal control group,model group,model+dexamethasone 4 mg·kg-1 group(before modeling,intragastric administration of saline was performed once daily for 6 d,followed by intragastric administration of dexamethasone 4 mg·kg-1 on days 7 and 8),model+riociguat 10 mg·kg-1 group(before modeling,intragastric administration once a day for 7 d),and model+sGC003 5 and 10 mg·kg-1 groups(before modeling,intragastric administration once a day for 7 d).All groups except the normal control group received intratracheal instillation of lipopolysaccharide at a dose of 4 mg·kg-11 h after drug administration on day 7,followed by placement in a hypoxic environment to establish the HAPE model.After 24 h of modeling,the expiratory time,end-inspiratory pause,enhanced pause,and breathing frequency were measured,Lung tissue morphology was examined using HE staining,and lung tissue edema was assessed by determining the wet to dry weight ratio(W/D).The level of interleukin-1β(IL-1β)was determined using immunofluorescence staining.The phosphorylation level of vasodilator-stimulated phosphoprotein(VASP)in lung tissue was analyzed by Western blotting.Additionally,levels of sGC,hypoxia inducible factor-1α(HIF-1α),cyclic guanosine monophosphate(cGMP),IL-6,and IL-1βin serum were quantified using ELISA.RESULTS Compared with the normal control group,the model group had obvious pulmonary edema,and the lung W/D,IL-1β levels,expiratory time,end-inspiratory pause,enhanced pause,as well as serum levels of IL-1β,HIF-1α and IL-6 were significantly increased.Concurrently,the frequency of breathing and serum levels of sGC and cGMP were significantly decreased.Compared with model group,the expiratory time,end-inspiratory pause,enhanced pause,lung W/D and IL-1β levels,and serum levels of IL-1β,HIF-1α and IL-6 were significantly decreased in the model+sGC003 10 mg·kg-1 group;while the frequency of breathing,serum sGC and cGMP levels,phosphorylation level of VASP in lung tissues were significantly increased.CONCLUSION sGC003 can improve lung function,suppress pulmonary inflammation,and mitigate pulmonary edema in HAPE mice by activating the sGC/cGMP pathway.

OBJECTIVE To investigate the anti-fatigue effect of chicory polysaccharide(CP)on mice exposed to simulated hypobaric hypoxia.METHODS Male C57BL/6J mice were randomly divided into the control group,model group,model+CP 150,300 and 600 mg·kg-1 groups.The control and model groups were given normal saline,while the CP groups were given drugs of different doses.After a 14 d pre-administration period,all the mice except the control group were exposed to a simulated alti-tude of 7 000 m in a hypobaric and hypoxic animal experimental chamber.After 7 d,a treadmill fatigue test was conducted to assess exercise endurance.The body weight and organ indexes were evaluated.The pathological changes in organs and tissues were observed via HE staining.The levels of fatigue-related and oxidative stress-related indicators were measured.The expression levels of phosphorylated AMP-activated protein kinase(p-AMPK),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),and cytochrome c oxidase Ⅳ(COXⅣ)were determined using Western blotting anal-ysis.RESULTS Compared with model group,exercise endurance was significantly enhanced,body weight and organ indexes improved,and pathological damage to the lung,liver and skeletal muscle mitigated in the model+CP 600 mg·kg-1 group.Compared with model group,the model+CP 600 mg·kg-1 group had the contents of serum lactate and blood urea nitrogen reduced,but the contents of glycogen and the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the liver and skeletal muscle were increased.The malondialdehyde content was lowered,but the expressions of p-AMPK,PGC-1α,and COXⅣ in skeletal muscle were significantly increased.CONCLUSION CP can alleviate altitude-induced fatigue by reducing the metabolite accumulation,increasing glycogen storage,and lowering oxidative stress levels.The underlying mechanism may involve the activation of the AMPK/PGC-1αsignaling pathway.

OBJECTIVE To investigate the role and mechanisms of the soluble guanylate cyclase(sGC)stimulator sGC003 in improving high altitude pulmonary edema(HAPE)in mice.METHODS Mice were randomly assigned to a normal control group,model group,model+dexamethasone 4 mg·kg-1 group(before modeling,intragastric administration of saline was performed once daily for 6 d,followed by intragastric administration of dexamethasone 4 mg·kg-1 on days 7 and 8),model+riociguat 10 mg·kg-1 group(before modeling,intragastric administration once a day for 7 d),and model+sGC003 5 and 10 mg·kg-1 groups(before modeling,intragastric administration once a day for 7 d).All groups except the normal control group received intratracheal instillation of lipopolysaccharide at a dose of 4 mg·kg-11 h after drug administration on day 7,followed by placement in a hypoxic environment to establish the HAPE model.After 24 h of modeling,the expiratory time,end-inspiratory pause,enhanced pause,and breathing frequency were measured,Lung tissue morphology was examined using HE staining,and lung tissue edema was assessed by determining the wet to dry weight ratio(W/D).The level of interleukin-1β(IL-1β)was determined using immunofluorescence staining.The phosphorylation level of vasodilator-stimulated phosphoprotein(VASP)in lung tissue was analyzed by Western blotting.Additionally,levels of sGC,hypoxia inducible factor-1α(HIF-1α),cyclic guanosine monophosphate(cGMP),IL-6,and IL-1βin serum were quantified using ELISA.RESULTS Compared with the normal control group,the model group had obvious pulmonary edema,and the lung W/D,IL-1β levels,expiratory time,end-inspiratory pause,enhanced pause,as well as serum levels of IL-1β,HIF-1α and IL-6 were significantly increased.Concurrently,the frequency of breathing and serum levels of sGC and cGMP were significantly decreased.Compared with model group,the expiratory time,end-inspiratory pause,enhanced pause,lung W/D and IL-1β levels,and serum levels of IL-1β,HIF-1α and IL-6 were significantly decreased in the model+sGC003 10 mg·kg-1 group;while the frequency of breathing,serum sGC and cGMP levels,phosphorylation level of VASP in lung tissues were significantly increased.CONCLUSION sGC003 can improve lung function,suppress pulmonary inflammation,and mitigate pulmonary edema in HAPE mice by activating the sGC/cGMP pathway.

OBJECTIVE To investigate the anti-fatigue effect of chicory polysaccharide(CP)on mice exposed to simulated hypobaric hypoxia.METHODS Male C57BL/6J mice were randomly divided into the control group,model group,model+CP 150,300 and 600 mg·kg-1 groups.The control and model groups were given normal saline,while the CP groups were given drugs of different doses.After a 14 d pre-administration period,all the mice except the control group were exposed to a simulated alti-tude of 7 000 m in a hypobaric and hypoxic animal experimental chamber.After 7 d,a treadmill fatigue test was conducted to assess exercise endurance.The body weight and organ indexes were evaluated.The pathological changes in organs and tissues were observed via HE staining.The levels of fatigue-related and oxidative stress-related indicators were measured.The expression levels of phosphorylated AMP-activated protein kinase(p-AMPK),peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α),and cytochrome c oxidase Ⅳ(COXⅣ)were determined using Western blotting anal-ysis.RESULTS Compared with model group,exercise endurance was significantly enhanced,body weight and organ indexes improved,and pathological damage to the lung,liver and skeletal muscle mitigated in the model+CP 600 mg·kg-1 group.Compared with model group,the model+CP 600 mg·kg-1 group had the contents of serum lactate and blood urea nitrogen reduced,but the contents of glycogen and the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in the liver and skeletal muscle were increased.The malondialdehyde content was lowered,but the expressions of p-AMPK,PGC-1α,and COXⅣ in skeletal muscle were significantly increased.CONCLUSION CP can alleviate altitude-induced fatigue by reducing the metabolite accumulation,increasing glycogen storage,and lowering oxidative stress levels.The underlying mechanism may involve the activation of the AMPK/PGC-1αsignaling pathway.

Objective To investigate the relationship between two-lung ventilation (TLV) with single-lumen endotracheal tube (SLT), one-lung ventilation (OLV) with double-lumen endotracheal tube (DLT) and postoperative pulmonary complications (PPCs) after total thoracoscopic cardiac surgery. Methods The clinical data of patients who underwent totally thoracoscopic cardiac surgeries in the Guangdong Provincial People’s Hospital from October 2019 to October 2021 were retrospectively analyzed. The patients were divided into 2 group according to the type of endotracheal tube, including a SLT group and a DLT group. Baseline data, surgical variables and PPCs were compared. The influencing factors of PPCs in the two groups were analyzed by binary logistic regression analysis. Results Finally 349 patients were enrolled, including 180 males and 169 females with an average age of (50.0±14.8) years. There were 219 patients in the SLT group and 130 patients in the DLT group. There was no statistical difference in baseline data, surgical variables or PPCs between the two groups (P＞0.05). Binary logistic regression analysis showed that PPCs were related to body mass index in the SLT group (OR=0.778, 95%CI 0.637 to 0.951, P=0.014) and preoperative smoking history in the DLT group (OR=0.058, 95%CI 0.004 to 0.903, P=0.042). Conclusion For the patients who undergo totally thoracoscopic cardiac surgery, TLV with SLT and OLV with DLT show no significant association with PPCs. At the same time, PPCs are associated with body mass index in the SLT group, while associated with preoperative smoking history in the DLT group.

Objective To analyze the modeling elements and subjects of the animal model of skin photoaging, and to provide a reference for the preparation and improvement of the model and a basis for the scientific evaluation of the subject.Methods By searching and collecting relevant literature on the preparation of animal models of skin photoaging from 2010 to 2022 in the China National Knowledge Infrastructure, Wanfang Database, and PubMed database, the model animal species, gender, modeling method, modeling cycle, radiation source and its distance from the modeling site, cumulative radiation volume, detection indicators, and subjects (drugs or treatments) recorded in the literature were collated and summarized, and a database was established for statistical analysis.Results 257 articles that met the inclusion criteria were selected. Among them, the most common animal model was SKH-1 hairless mice, followed by SD rats and KM mice; the gender of animals was mainly female, medium-wave ultraviolet B (UVB) was often used as the radiation source, the distance between the radiation source and the modelling site was mostly 30 cm, and the modelling period was usually 40-60 days. The cumulative dose of long-wave ultraviolet A (UVA) was between 100-150 J/cm², and the cumulative dose of UVB was between 5-10 J/cm². The tests used after model establishment were skin histopathological examination, skin tissue homogenization, fibre staining, immunoblotting, etc. Subjects included Chinese herbal medicines, Chinese herbal extracts, Chinese patent medicines, Chinese herbal compound medicines, chemical drugs, biological agents and other treatments, while the animal model of skin photoaging was also used for clinical efficacy studies of external Chinese medicine, physiotherapy and positive control drugs.Conclusion In skin photoaging animal experiments, female SKH-1 hairless mice are often used, and UVB is used as the radiation source. The modeling period is usually 40-60 days, and the minimum erythema dose (MED) is incremented week by week. The cumulative UVB irradiation dose ranges from 0 to 10 J/cm², which has the advantages of high success rate, good reproducibility and high similarity with clinical disease.

Objective To observe the effects of dietary nursing based on macroscopic and microscopic syndrome differentiation on the compliance, clinical efficacy and quality of life (QOL) of ulcerative colitis patients with damp-heat in large intestine. Methods One hundred and ten cases meeting the diagnostic criteria of ulcerative colitis patients with damp-heat in large intestine were divided into routine group and observation group, 55 cases in each group. Both groups were given oral use of Sulfasalazine Tablets, and routine health education and dietary nursing for ulcerative colitis patients with damp-heat in large intestine. Additionally, the observation group was given dietary nursing based on macroscopic syndrome differentiation and colonoscopic microscopic syndrome differentiation. One month constituted a treatment course. After 6 courses of treatment, the compliance, clinical efficacy and QOL of the two groups were compared. Results (1) The incidence of medication missing or suspension in the routine group was 14.55%, while the incidence of diet missing or suspension in the observation group was 1.82%, the difference between the two groups being statistically significant (P < 0.01). (2) In the routine group, the cure rate was 5.5% and the total effective rate was 81.8%; in the observation group, the cure rate was 12.7% and the total effective rate was 92.7%. The differences between the two groups were statistically significant(P<0.05).(3) The scores of each dimension of QOL scale in the observation group were higher than those of the routine group (P < 0.05) , indicating that the improvement of QOL in the observation group was superior to that of the routine group. Conclusion The compliance, clinical efficacy and QOL of ulcerative colitis patients with damp-heat in large intestine are enhanced after treatment with dietary nursing based onmacroscopic and microscopic syndrome differentiation.

Objective To investigate the efficacy and safety of 6-month and 12-month oral dual-antiplatelet therapy This work was supported by the National Key Technology Research and Development Program in the Twelfth Five-year Plan of China (2011BAIl1B07) and the Military Clinical Key Technology and Development Program (2010gxjs001)(DAPT) on patients implanted with biodegradable polymer-coated and drug-eluted long stents (BP-DES).Methods In the I-LOVE-IT 2 trial,574 patients implanted with biodegradable polymer-coated and sirolimus-eluted long stent (BP-SES) (total stent length ≥50mm) were randomized to accepting either 6-month (n=270) or 12-month (n=304) DAPT.The primary endpoint of present study was 12-month target lesion failure (TLF),including cardiac death,target vessel myocardial infarction and clinically indicated target lesion revascularization (CI-TLR).The major secondary endpoint was 12-month net adverse clinical events (NACE),including all-causes of death,myocardial infarction,stroke,all revascularization (CI-TLR plus clinically indicated nontarget lesion revascularization) and bleeding.Results For the patients implanted with BP-SES of total stent length≥ 50mm,the total stent length was 73.0 ± 22.5mm and 69.8 ± 19.4mm in the 6-month DAPT group and 12-month group,respectively (P=0.07).No significant difference existed in the incidence of 12-month TLF between 6-month DAPT group and 12-month DAPT group (11.1％ vs.9.2％,P=0.47).The incidence of NACE was similar between the 2 groups (21.9％ vs.19.7％,P=0.57).The incidence of revascularization was lower in 12-month DAPT group (5.6％) than in 6-month DAPT group (11.1％,P=0.01).Furthermore,6-month landmark analysis showed that 12-month DAPT was associated with significantly lower risk of TLF (2.6％ vs.6.3％,P=0.03) at a cost of slightly increased risk of all bleeding events (1.6％ vs.0.7％,Log-rank P=0.32) between 6 and 12-months compared to 6-month DAPT.Conclusions In patients treated with BP-SES of total stent length ≥ 50mm,12-month DAPT have similar impacts on 12-month clinical outcomes except for all revascularization.However,12 months DAPT decreased the incidence of TLF and total revascularization between 6 months to 12 months after PCI.

BACKGROUND: Critical closing pressure (CCP) is recently thought to play a key role in cerebral blood flow autoregulation as an effective downstream pressure of cerebral circulation and can objectively reflect the cerebrovascular tone, namely the vascular smooth muscle contraction and diastole, which is subjected to dynamic modulation.OBJECTIVE: To dynamically assess the hypertension-induced damage of the contraction function of cerebral microvascular smooth muscles and its correlation with morphological changes based on CCP evaluation.DESIGN: Randomized controlled experiment.SETTING: Institute of Neural Science of Second Hospital Affiliated to Guangzhou Medical College and Department of Neurology, First Hospital Affiliated to Sun Yet-san University.MATERIALS: The experiment was carried out at the Laboratory of Physiological Science of Sun Yet-san University between July 2002 and August 2003. Totally 160 health male SD rats were randomized into control group and hypertension group with 80 rats in each group. METHODS: Stroke-prone renovas cular hyp ortonsive rats were established in rats of the hypertension group by bilateral renal artery occlusion with two clips. The rats in the control group were not subjected to the occlusion with other treatments identical to those of the hypertension group. At the time points of 2, 4, 6, 8, 10, 12, 14 and 16 weeks after operation, respectively, 10 rats were randomly selected from each of the two groups for determination of arterial pressure and CCP. After the measurements the frontal-parietal lobe was obtained from the anaesthetized rats and cut into slices for quantitative analysis of the morphological changes in cerebral microvessels.different postoperative time points.mean arterial pressure in hypertension group obviously increased from the 6th postoperative week with significant difference from that of the control after operation to a level significantly higher than that of the control group at postoperative 14 and 16 weeks [(63.75±7.43) vs (37.28±3.68) mm Hg and (67.37±15.57) vs (38.39t7.41) mm Hg, respectively, P ＜ 0.05].significance from that of the control group at the 8th postoperative week (Paverage arterial pressure and cerebral arteriole tunica media (r=0.906 93,0.811 36, respectively, P ＜ 0.05). The changes in CCP was more obvious in the early and advanced stages of blood pressure elevation, but not so manifest during obvious blood pressure increment, displaying an inverted S-shaped curve of changes (R2=0.996 2, P ＜ 0.05).CONCLUSION: Contraction of the cerebrovascular smooth muscles is enhanced with the dynamic increment of arterial pressure after the development of hypertension. Vascular tone increase is more manifest during the early and advanced stages of hypertension.