AIM:This study aimed to explore the mechanism by which Bufei-Yishen formula(BYF)mitigates mitochondrial damage in rats with chronic obstructive pulmonary disease(COPD)by regulating the AMPK/PGC-1α signal-ing pathway.METHODS:Forty rats were randomly divided into four groups,each containing ten rats each:control group,COPD group,BYF group,and N-acetylcysteine(NAC)group.The COPD model was established through chronic cigarette smoke exposure combined with periodic bacterial inoculations over an eight-week induction phase.During the subsequent eight-week treatment period(i.e.,weeks 9～16),rats in the control and COPD groups received an isovolumet-ric saline solution via oral gavage,at a standardized daily dose of 2 mL per animal.Moreover,rats in the BYF and NAC groups were given Bufei Yishen formula(11.61 g·kg-1·d-1)or N-acetylcysteine(54 mg·kg-1·d-1)by gavage,once per day.At week 16,samples were collected and the general condition of the rats was observed.Body weight was recorded weekly.We also obtained data characterizing rat lung function,lung pathology,ATP content,and mitochondrial ultra-structure,as well as the levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),se-rum transforming growth factor-beta 1(TGF-β1)and the enzymatic activities of mitochondrial electron transport chain complexes I(NADH dehydrogenase)and III(cytochrome c reductase).Finally,we quantified the mRNA and protein lev-els of AMPK and PGC-1α in lung tissue.RESULTS:Compared to the control group,the COPD group exhibited yellow-ish hair color,reduced gloss,slower weight gain,and a disordered respiratory rhythm.We also observed significant de-creases(P<0.01)in pulmonary function tidal volume(TV),minute ventilation(MV),peak expiratory flow(PEF),expi-ratory flow at 50%of tidal volume(EF50),forced vital capacity(FVC),forced expiratory volume in 0.1 s(FEV0.1),and FEV0.1/FVC.Histopathological analysis showed alveolar cavity enlargement,bullous changes in lung morphology,smooth muscle hypertrophy in the tracheal wall,ciliary destroyed,mucosal shrinking and thickening,and a large number of in-flammatory cells gathered around the tube.Moreover,the mean linear intercept(MLI)and bronchial wall thickness(BWt)had both significantly increased(P<0.01).Electron microscopic analysis of the lungs revealed a reduction in the number of mitochondria in alveolar epithelial cells,a swollen and deformed lung morphology overall.We observed that the mitochondrial cristae were broken,dissolved or vacuolated,accompanied by a significant reduction in the number of lamel-lar bodies and lung volume,along with a disordered internal lipid layer structure.Furthermore,some lung samples were vacuolated or had content leakage.Further quantitative analyses showed statistically significant increases(P<0.01)in the levels of serum pro-inflammatory mediators,including IL-6,TNF-α,IL-1β,and TGF-β1.At the same time we observed substantial reductions in the enzymatic activities of mitochondrial electron transport chain complexes I and III(P<0.01).Moreover,we found that metabolic impairment correlated with significantly attenuated ATP production(P<0.01)in exper-imental subjects.Moreover,the expression levels of AMPK and PGC-1α mRNA and proteins in lung tissue were signifi-cantly decreased(P<0.01).Moreover,compared to the COPD group,the BYF group showed significant improvements in several of the above indicators,albeit to different degrees(P<0.01 or P<0.05).Moreover,BYF was more effective than NAC in improving minute ventilation and up-regulating PGC-1α expression(P<0.05).CONCLUSION:Bufei-Yishen formula may ameliorate mitochondrial damage in rats with chronic obstructive pulmonary disease by regulating the AMPK/PGC-1α signaling pathway.

BACKGROUND:After total knee arthroplasty,patients may experience significant pain,which has negative effects on functional recovery.Exploring and seeking effective means of analgesia has important clinical value.OBJECTIVE:To explore an effective perioperative analgesic strategy for total knee arthroplasty patients,we first proposed a novel local infiltration anesthetic formulation consisting of morphine,flurbiprofen,and compound betamethasone,and we explored its efficacy and safety.METHODS:This study retrospectively analyzed the clinical data of 60 patients who underwent unilateral total knee arthroplasty at First Affiliated Hospital of Anhui Medical University from January 2023 to April 2024.Based on whether local anesthesia was used during surgery,the patients were divided into the control and study groups,each consisting of 30 cases.In the study group,the local infiltration anesthesia mixture consisting of morphine,flurbiprofen,and compound betamethasone was injected into the joint cavity around the knee during surgery.No analgesic drugs were used in the control group as a blank control.We recorded and compared the postoperative visual analog scale pain scores,knee range of motion,knee function score,degree of postoperative knee edema,and incidence of postoperative complications between the two groups at different time points.RESULTS AND CONCLUSION:(1)Compared with the control group,the visual analog scale pain score in the study group was lower at 6,12,and 24 hours after operation,and the difference was statistically significant(Z=-2.367,-2.906,-4.199,P＜0.05).However,there was no significant difference in the pain visual analog scale score between the two groups at 48 and 72 hours after operation(Z=-1.287,-1.478,P＞0.05).(2)The postoperative knee range of motion and knee function score of the study group were better than those of the control group,and the difference was statistically significant(t=-2.519,-8.027,P＜0.05).(3)The degree of knee joint swelling in the study group was also lighter than that in the control group,and the difference was statistically significant(Z=-2.818,P＜0.05).(4)In the early postoperative period,there was no significant difference in fever between the two groups(P＞0.05).There was no poor wound healing or periprosthetic infection in the two groups.(5)The results show that applying local infiltration anesthesia composed of morphine,flurbiprofen axetil,and compound betamethasone in total knee arthroplasty can relieve early postoperative pain and show high safety.However,prospective studies with large samples are still needed to provide data support.

ObjectiveTo evaluate the overall dietary intake of adult residents in Sijing Town, Songjiang District, Shanghai, and to explore the association between dietary health literacy and diet quality. MethodsA total of 1 280 adult residents were selected as the research subjects using a multi-stage sampling method, and face-to-face questionnaire surveys were administered on site. Dietary intake data were collected using a Food Frequency Questionnaire (FFQ), and the overall diet quality of the participants was evaluated based on the Chinese Healthy Eating Index (CHEI). Participants were divided into low- and high-CHEI groups according to the median CHEI score. Logistic regression models were used to examine the association between dietary health literacy and diet quality. ResultsThe median CHEI score for adults in the area was 63.68 points. Multivariate logistic regression analysis revealed that adults with lower dietary health literacy had lower CHEI scores and poorer overall diet quality compared to those with higher dietary health literacy (OR=1.435, 95%CI:1.132‒1.819). ConclusionThe overall diet quality of adult residents in this region requires improvement. There is a significant positive correlation between the level of dietary health literacy and CHEI scores, suggesting that enhancing dietary health literacy may be an important strategy to improve resident’ dietary quality.

OBJECTIVES: To evaluate the protective effect of Bufei Yishen Formula (BYF) against cigarette smoke extract (CSE)-induced injuries in human bronchial epithelial BEAS-2B cells and explore the underlying mechanism. METHODS: BEAS-2B cells exposed to CSE were treated with normal rat serum, BYF-medicated rat serum at low or high doses, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), PDTC combined with high-dose BYF-medicated serum, or S-carbomethyloysteine (S-CMC, as the positive control). CCK-8 assay was used to determine the optimal concentration and treatment time of CSE, BYF-medicated serum and S-CMC. The treated cells were examined for inflammatory factor levels in the supernatant and cellular expressions of MUC5AC and MUC5B using ELISA, cell ultrastructural changes with transmission electron microscopy, and cell apoptosis rate using flow cytometry. The expression levels of TLR4/NF‑κB pathway-associated mRNAs and proteins were determined by qRT-PCR and Western blotting. RESULTS: CSE exposure significantly increased secretions of IL-1β, IL-6 and TNF-α, mRNA and protein expressions of MUC5AC and MUC5B, and early and total apoptosis rates in BEAS-2B cells, where the presence of apoptotic bodies was detected. CSE also significantly enhanced the mRNA and protein expressions of TLR4, I-κB, and NF-κB and reduced mRNA and protein expressions of AQP5. Treatments of the CSE-exposed cells with BYF-medicated serum, PDTC and S-CMC all significantly lowered inflammatory factor levels, MUC5AC and MUC5B expressions, and early and total cell apoptosis rates, and partly reversed the changes in cellular ultrastructure and mRNA and protein expressions of the TLR4/NF-κB pathway, and the effects were the most conspicuous following the combined treatment with high-dose BYF-medicated serum and PDTC. CONCLUSIONS BYF can inhibit cell apoptosis, inflammation and mucus hypersecretion in CSE-induced BEAS-2B cells by inhibiting the TLR4/NF-κB signaling pathway.
Humans ; Epithelial Cells/cytology* ; Drugs, Chinese Herbal/pharmacology* ; NF-kappa B/metabolism* ; Bronchi/cytology* ; Smoke/adverse effects* ; Apoptosis/drug effects* ; Mucin 5AC/metabolism* ; Cell Line ; Toll-Like Receptor 4/metabolism* ; Mucin-5B/metabolism* ; Signal Transduction/drug effects* ; Nicotiana ; Rats ; Thiocarbamates/pharmacology* ; Animals

AIM:This study aimed to explore the mechanism by which Bufei-Yishen formula(BYF)mitigates mitochondrial damage in rats with chronic obstructive pulmonary disease(COPD)by regulating the AMPK/PGC-1α signal-ing pathway.METHODS:Forty rats were randomly divided into four groups,each containing ten rats each:control group,COPD group,BYF group,and N-acetylcysteine(NAC)group.The COPD model was established through chronic cigarette smoke exposure combined with periodic bacterial inoculations over an eight-week induction phase.During the subsequent eight-week treatment period(i.e.,weeks 9～16),rats in the control and COPD groups received an isovolumet-ric saline solution via oral gavage,at a standardized daily dose of 2 mL per animal.Moreover,rats in the BYF and NAC groups were given Bufei Yishen formula(11.61 g·kg-1·d-1)or N-acetylcysteine(54 mg·kg-1·d-1)by gavage,once per day.At week 16,samples were collected and the general condition of the rats was observed.Body weight was recorded weekly.We also obtained data characterizing rat lung function,lung pathology,ATP content,and mitochondrial ultra-structure,as well as the levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),se-rum transforming growth factor-beta 1(TGF-β1)and the enzymatic activities of mitochondrial electron transport chain complexes I(NADH dehydrogenase)and III(cytochrome c reductase).Finally,we quantified the mRNA and protein lev-els of AMPK and PGC-1α in lung tissue.RESULTS:Compared to the control group,the COPD group exhibited yellow-ish hair color,reduced gloss,slower weight gain,and a disordered respiratory rhythm.We also observed significant de-creases(P<0.01)in pulmonary function tidal volume(TV),minute ventilation(MV),peak expiratory flow(PEF),expi-ratory flow at 50%of tidal volume(EF50),forced vital capacity(FVC),forced expiratory volume in 0.1 s(FEV0.1),and FEV0.1/FVC.Histopathological analysis showed alveolar cavity enlargement,bullous changes in lung morphology,smooth muscle hypertrophy in the tracheal wall,ciliary destroyed,mucosal shrinking and thickening,and a large number of in-flammatory cells gathered around the tube.Moreover,the mean linear intercept(MLI)and bronchial wall thickness(BWt)had both significantly increased(P<0.01).Electron microscopic analysis of the lungs revealed a reduction in the number of mitochondria in alveolar epithelial cells,a swollen and deformed lung morphology overall.We observed that the mitochondrial cristae were broken,dissolved or vacuolated,accompanied by a significant reduction in the number of lamel-lar bodies and lung volume,along with a disordered internal lipid layer structure.Furthermore,some lung samples were vacuolated or had content leakage.Further quantitative analyses showed statistically significant increases(P<0.01)in the levels of serum pro-inflammatory mediators,including IL-6,TNF-α,IL-1β,and TGF-β1.At the same time we observed substantial reductions in the enzymatic activities of mitochondrial electron transport chain complexes I and III(P<0.01).Moreover,we found that metabolic impairment correlated with significantly attenuated ATP production(P<0.01)in exper-imental subjects.Moreover,the expression levels of AMPK and PGC-1α mRNA and proteins in lung tissue were signifi-cantly decreased(P<0.01).Moreover,compared to the COPD group,the BYF group showed significant improvements in several of the above indicators,albeit to different degrees(P<0.01 or P<0.05).Moreover,BYF was more effective than NAC in improving minute ventilation and up-regulating PGC-1α expression(P<0.05).CONCLUSION:Bufei-Yishen formula may ameliorate mitochondrial damage in rats with chronic obstructive pulmonary disease by regulating the AMPK/PGC-1α signaling pathway.

BACKGROUND:After total knee arthroplasty,patients may experience significant pain,which has negative effects on functional recovery.Exploring and seeking effective means of analgesia has important clinical value.OBJECTIVE:To explore an effective perioperative analgesic strategy for total knee arthroplasty patients,we first proposed a novel local infiltration anesthetic formulation consisting of morphine,flurbiprofen,and compound betamethasone,and we explored its efficacy and safety.METHODS:This study retrospectively analyzed the clinical data of 60 patients who underwent unilateral total knee arthroplasty at First Affiliated Hospital of Anhui Medical University from January 2023 to April 2024.Based on whether local anesthesia was used during surgery,the patients were divided into the control and study groups,each consisting of 30 cases.In the study group,the local infiltration anesthesia mixture consisting of morphine,flurbiprofen,and compound betamethasone was injected into the joint cavity around the knee during surgery.No analgesic drugs were used in the control group as a blank control.We recorded and compared the postoperative visual analog scale pain scores,knee range of motion,knee function score,degree of postoperative knee edema,and incidence of postoperative complications between the two groups at different time points.RESULTS AND CONCLUSION:(1)Compared with the control group,the visual analog scale pain score in the study group was lower at 6,12,and 24 hours after operation,and the difference was statistically significant(Z=-2.367,-2.906,-4.199,P＜0.05).However,there was no significant difference in the pain visual analog scale score between the two groups at 48 and 72 hours after operation(Z=-1.287,-1.478,P＞0.05).(2)The postoperative knee range of motion and knee function score of the study group were better than those of the control group,and the difference was statistically significant(t=-2.519,-8.027,P＜0.05).(3)The degree of knee joint swelling in the study group was also lighter than that in the control group,and the difference was statistically significant(Z=-2.818,P＜0.05).(4)In the early postoperative period,there was no significant difference in fever between the two groups(P＞0.05).There was no poor wound healing or periprosthetic infection in the two groups.(5)The results show that applying local infiltration anesthesia composed of morphine,flurbiprofen axetil,and compound betamethasone in total knee arthroplasty can relieve early postoperative pain and show high safety.However,prospective studies with large samples are still needed to provide data support.

Chronic obstructive pulmonary disease(COPD)is a disease characterized by persistent respiratory symptoms and airflow limitation,and also associated with a variety of comorbidities.As one of the important extrapulmonary comorbidities of COPD,kidney injury has a high incidence and insidious onset,which will develop into chronic kidney disease without timely intervention,greatly increasing the risk of mortality and economic burden of COPD patients.There exist physiological and pathological relations between lung and kidney functions.However,the mechanisms underlying COPD-associated kidney injury remain unclear.This article provides a review of the research progress on the mechanisms of COPD-associated kidney injury,in order to provide reference for the clinical prevention and treatment and basic research.

AIM:To investigate the effects of the three Tiao-Bu Fei-Shen therapies on renal injury in rats with chronic obstructive pulmonary disease(COPD),and to explore the mechanisms.METHODS:SPF-grade SD rats were randomly divided into control,COPD,pyrrolidinedithiocarbamate ammonium(PDTC),Bufei-Jianpi formula(BJF),Bu-fei-Yishen formula(BYF),Yiqi-Zishen formula(YZF),BJF combined with PDTC(BJF+PDTC),BYF combined PDTC(BYF+PDTC),and YZF combined PDTC(YZF+PDTC)groups.Cigarette smoke exposure combined with bacterial infec-tion were used to develop a stable-phase rat model of COPD,and kidney-injured rats were screened for subsequent treat-ment.Pulmonary and renal functions,pathological changes in lung and kidney tissues,24 h urine volume,urine biochem-ical indexes,aquaporin(AQP)levels,ratio of inflammatory cells in the bronchoalveolar lavage fluid(BALF),serum in-flammatory factor levels,and mRNA and protein expressions of IκB kinase(IKK)and nuclear factor-κB(NF-κB)were observed at the end of the 16th week.RESULTS:Compared with control group,the rats in COPD group showed reduced lung function indexes of forced expiratory vital capacity(FVC),forced expiratory volume in 0.1 second(FEV0.1)and FEV0.1/FVC(P<0.05).The lung histopathology exhibited alveolar wall fracture and fusion and airway inflammatory cell infiltration.The renal function indexes serum creatinine,blood urea nitrogen and serum cystatin C(Cys-C)were signifi-cantly increased(P<0.01).The renal histopathology showed swollen and disorderly arranged tubular epithelial cells.The 24 h urine volume decreased(P<0.01).The urinary biochemical indexes 24 h urinary total protein,urinary kidney injury molecule-1(KIM-1),urinary Cys-C,and urinary N-acetyl-β-D-glucosaminidase significantly increased(P<0.01).The protein levels of AQP1～4 were significantly increased(P<0.01).The ratio of neutrophils and lymphocytes in the BALF were increased(P<0.01).The ratio of monocytes was decreased(P<0.01).The serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-13,IL-1β,and transforming growth factor-β1(TGF-β1)were significantly increased(P<0.01).And the mRNA and protein expression levels of IKK,NF-κB were significantly elevated in the renal tissue(P<0.05).Compared with COPD group,the above symptoms and indexes of the rats were improved to different degrees after the intervention in treatment groups,among which BJF,BYF and YZF demonstrated similar effects to PDTC,and BJF+PDTC,BYF+PDTC and YZF+PDTC exhibited better improvements than the corresponding monotherapy.CONCLU-SION:The three Tiao-Bu Fei-Shen therapies can reduce the airway and systemic inflammatory response,improve renal function and attenuate renal injury in COPD rats.The mechanism may be related to the inhibition of NF-κB signaling path-way.

Objective To investigate the mechanism by which Xuanfei Jiedu Formula(XFJDF)ameliorates pulmonary damage in rats with multidrug-resistant Pseudomonas aeruginosa(MDR-PA)pneumonia,by modulating the activity of the inhibitor of nuclear factor(NF)-κB kinase(IKK)IKK/NF-κB signal transduction cascade.Methods Eighty-four rats were divided randomly into seven groups:control,model,XFJDF-low dose,XFJDF-medium dose,XFJDF-high dose,imipenem(IPM),and pyrrolidinedithiocarbamate ammonium(PDTC)groups(n=12 rats per group).A MDR-PA pneumonia rat model was established by oral tracheal intubation.After successful model construction,rats in the low-,medium-,and high-dose XFJDF groups were given the corresponding dose of drugs by gavage,rats in the IPM group were given an intraperitoneal injection of IPM,and rats in the control and model groups were given the same volume of normal saline by gavage,twice a day for 7 days.PDTC was injected intraperitoneally 1 h before model establishment,12 h and 24 h after model establishment in the NF-κB inhibitor group.The behavior status,body weight changes,spleen and thymus indexes,and lung wet weight/dry weight ratio were observed in the different groups.Histological changes in the lung tissue were assessed by hematoxylin and eosin staining.Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to detect apoptosis of lung tissue cells,and serum levels of interleukin(IL)-1 β,tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β,and IL-10 were detected by enzyme-linked immunosorbent assay,and glutathione(GSH)and malondialdehyde(MDA)levels,myeloperoxidase(MPO)activity and total antioxidant capacity(T-AOC)were determined by colorimetry and thiobarbituric acid assay.NF-κBp65 in lung tissue was identified by immunohistochemical analysis,IKKβ and NF-κBp65 mRNA were analyzed by reverse transcription quantitative polymerase chain reaction,and expression levels of IKKβ,phosphorylated(p)-IKKβ,NF-κBp65,and p-NF-κBp65 were measured by Western blot.Results Compared with the control group,rats in the model group exhibited decreased appetite,dull fur,sluggish responsiveness,decreased mobility,increased respiratory rate,audible murmurs,and notable weight loss(P＜0.01).The spleen and thymus indices were significantly enhanced(P＜0.01)and the lung wet/dry weight ratio was significantly increased(P＜0.01),concurrent with increased alveolar secretions in lung tissue.Infiltration of abundant inflammatory cells and increased apoptosis in lung tissue were also noted.Serum concentrations of IL-1β,TNF-α,TGF-β,and IL-10 were increased(P＜0.01)and the MDA content and MPO activity were also increased(P＜0.01).Conversely,GSH levels and T-AOC were significantly decreased(P＜0.01).Lung levels of IKKβ and NF-κBp65 mRNA were significantly increased(P＜0.01)and the ratios of p-IKKβ/IKKβ and p-NF-κBp65/NF-κBp65 were also significantly increased(P＜0.01)compared with the control group.XFJDF,IPM and PDTC improved these parameters to varying degrees,compared with the model group(P＜0.05,P＜0.01),with particularly significant effects in the high-dose XFJDF and IPM groups.Conclusions XFJDF may improve lung injury in rats with MDR-PA pneumonia by inhibiting the IKK/NF-κB signaling pathway.

OBJECTIVE To investigate the impact of the methionine synthase reductase （MTRR） rs10380 C＞T gene polymorphism on methotrexate （MTX） plasma concentration， adverse drug reaction， and prognosis in children with intracranial tumors. METHODS Peripheral blood was collected from children with intracranial tumors， and genomic DNA was extracted. The MTRR rs10380 C＞T genotype was analyzed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. The association of the MTRR rs10380 C＞T gene polymorphism with the ratio of MTX plasma concentration to dose （C/D ratio）， adverse drug reaction， tumor recurrence， and metastasis was analyzed. Bioinformatics analysis was used to explore the association of the rs10380 genotype and MTRR gene expression and its possible mechanisms. RESULTS A total of 75 children were included in the study. The distribution frequencies of the wild-type CC genotype and C allele of rs10380 were 62.67% and 81.33%， respectively， while the distribution frequencies of the variant CT genotype and T allele were 37.33% and 18.67%， respectively， which were in accordance with Hardy-Weinberg equilibrium（P＞0.05）. The incidence of electrolyte disorders （51.06%） and tumor metastasis rate （57.45%） in children with the CC genotype were significantly higher than those with the CT genotype （P＜0.05）. No significant differences were observed in the 24-hour and 42-hour C/D ratios and recurrence rates between the two genotypes of children （P＞0.05）. Bioinformatics analysis showed that MTRR protein mainly works in conjunction with 10 proteins， including MMAA， and was involved in various biological processes such as sulfur amino acid biosynthesis. CONCLUSIONS The MTRR rs10380 CC genotype may be a risk factor for electrolyte disorders and tumor metastasis in children with intracranial tumors after MTX chemotherapy.