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:Bushen Zhuanggu Formula(BZF),derived from the classic Yougui Pills,has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head(NONFH),particularly by promoting bone repair.However,its underlying mechanisms remain unclear.Objective:This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH.Materials and methods:A total of 518 potential BZF targets were identified from the ETCM v2.0 database.Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls.A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis.In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH.Results:Network analysis identified key pathways associated with blood circulation obstruction,immune-inflammatory imbalance,and abnormal bone metabolism.Protein kinase C alpha(PKCA),Ras proto-oncogene(RAS),mitogen-activated protein kinase 3(ERK),ETS proto-oncogene 1(ETS1),and receptor activator of nuclear factor-κB ligand(RANKL)formed a signaling axis implicated in NONFH pathogenesis.BZF treatment alleviated joint inflammation,preserved trabecular bone morphology,reduced bone loss,and promoted bone repair.Mechanistically,BZF significantly downregulated the expression of PKCA,RAS,ERK,ETS1,and RANKL,improved blood circulation,and inhibited osteoclast activation while promoting osteoblast activation.Conclusion:BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis,thereby reversing dysregulated bone metabolism.

Objective A Cobb angle prediction model for adolescent idiopathic scoliosis(AIS)based on three-point mechanical data from three-dimensional(3D)-printed orthotics and various machine learning algorithms was developed,so as to provide an innovative,radiation-free method for early clinical screening and monitoring of AIS.Methods Clinical data from AIS patients and mechanical data from 3D-printed orthotics were collected to construct a comprehensive dataset with features such as gender,age,disease type,weight,and Risser score.Six algorithms,namely,random forest,support vector regression,gradient boosting regressor,extreme gradient boosting,lightgbm,and catboost,were used to construct and evaluate the performance of Cobb angle prediction models.Results The gradient boosting regressor model had the best performance on several evaluation metrics,achieving a precision rate of 0.937,recall rate of 0.818,F1-score of 0.949,and an area under curve(AUC)value of 0.843.In the validation set,the model's predictions reached an accuracy rate of 0.942,fitting well with the actual Cobb values.Conclusions The Cobb angle prediction model based on mechanical data and machine learning effectively avoids the radiation risks associated with traditional full-spine X-ray examinations in early clinical screening.It provides a non-invasive assessment for AIS patients,enhancing the safety and efficiency of screening and monitoring,and offering a powerful decision-making tool for clinicians,with a great clinical significance.

Objective:To investigate the differences between high-frequency ultrasound-guided manual detorsion combined with surgery(MD+S)and surgery alone in the treatment of testicular torsion,and to provide some new evidence for the timely diagno-sis and treatment of the disease.Methods:We retrospectively analyzed the clinical data on 134 cases of unilateral testicular torsion within 48 hours treated in our hospital by MD+S or by surgery alone from January 2015 to May 2022.We statistically analyzed the age distribution,and duration and degrees of testicular torsion,followed by comparison between the two groups.Results:In the 134 ca-ses,the median age of onset was 15(13-19)years old,the median onset-to-visit time was 15(8-25)hours,and the median de-gree of torsion was 360°(180°-1080°).Of the total number of patients,21 underwent testicular excision and the other 113 were treated with the testis preserved,with no statistically significant difference in age distribution between the two groups(P＞0.05),and a higher rate of testis resection in those with longer duration and greater angle of torsion(P＜0.05).Totally,33 of the patients were assigned to the MD+S group and 101 to the surgery alone group.According to the actual clinical conditions and excluding those with torsion time longer than 24 hours and torsion angle greater than 720 °,28 of the patients underwent ultrasound-guided MD+S(with 1 case of testis resection,3.6％),and 68 received surgery alone(with 7 cases of testis resection,10.3％).The rate of testis resection was higher in the surgery alone than that in the MD+S group,but with no statistically significant difference between the two groups(P＞0.05),which was considered to be related to the small sample size in this study.Conclusion:The popularization of testicular torsion knowledge can shorten the onset-to-visit time,and reasonable manual detorsion before emergency surgery can reduce the rate of testis resection.

Objective A Cobb angle prediction model for adolescent idiopathic scoliosis(AIS)based on three-point mechanical data from three-dimensional(3D)-printed orthotics and various machine learning algorithms was developed,so as to provide an innovative,radiation-free method for early clinical screening and monitoring of AIS.Methods Clinical data from AIS patients and mechanical data from 3D-printed orthotics were collected to construct a comprehensive dataset with features such as gender,age,disease type,weight,and Risser score.Six algorithms,namely,random forest,support vector regression,gradient boosting regressor,extreme gradient boosting,lightgbm,and catboost,were used to construct and evaluate the performance of Cobb angle prediction models.Results The gradient boosting regressor model had the best performance on several evaluation metrics,achieving a precision rate of 0.937,recall rate of 0.818,F1-score of 0.949,and an area under curve(AUC)value of 0.843.In the validation set,the model's predictions reached an accuracy rate of 0.942,fitting well with the actual Cobb values.Conclusions The Cobb angle prediction model based on mechanical data and machine learning effectively avoids the radiation risks associated with traditional full-spine X-ray examinations in early clinical screening.It provides a non-invasive assessment for AIS patients,enhancing the safety and efficiency of screening and monitoring,and offering a powerful decision-making tool for clinicians,with a great clinical significance.

Objective To study the effects of Hedysarum polysaccharides polysaccharide(HPS)on the farnesoid X receptor(FXR)-fibroblast growth factor-19(FGF19)signaling pathway of diabetes rats.Methods Twelve Wistar male rats were randomly selected as the normal group,and the other rats were fed with a single intraperitoneal injection of streptozotocin(50 mg·kg-1 STZ)and a high sugar and high-fat diet to replicate the diabetes rat model.Model rats were randomly divided into model group,positive control group(given 400 mg·kg-1·d-1 suspension of Bifidobacterium quadruplex live bacterial tablets by gavage),experimental-H,-M,-L groups(given 200,100,and 50 mg·kg-1·d-1 doses of HPS suspension by gavage);normal group,and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks.Glucose(Glu)was detected by a blood glucose meter;and serum total glyceride(TG)and total cholesterol(TC)were detected by enzyme-linked immunosorbent assay reagent kit;the expressions of FXR、fibroblast growth factor receptors 4(FGFR4)relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.Results The Glu concentrations in the normal group,model group,positive control group,and experimental-H groups were(7.66±0.61),(29.25±1.64),(23.31±3.02)and(19.31±5.13)mmol·L-1,respectively;the TG content were(957.00±113.73),(1 345.00±246.44),(958.00±96.53)and(964.00±130.22)μmol·L-1,respectively;the TC content were(161.65±4.53),(302.19±5.35),(236.09±5.14)and(165.58±2.58)μmol·L-1,respectively;the expression of FXR relative mRNA expression level were 1.00±0.06,0.48±0.02,0.67±0.04 and 0.92±0.04,respectively;the expression of FGFR4 relative mRNA expression level were 1.00±0.04,0.17±0.01,0.48±0.04 and 0.41±0.03;respectively.The above indexes of the model group were compared with the control group,and the above indexes of the control group and the experimental-H group were compared with the model group,and the differences were statistically significant(all P＜0.01).Conclusion HPS improves blood sugar,lowers blood lipids,and protects liver and intestinal tissues,possibly by regulating the FXR-FGF19 signaling pathway in intestinal tissue,and regulating bile acid synthesis.

Objective To investigate how dietary supplementation with tetrahydrocurcumin(THC)improves kidney injury in type 2 dia-betic mellitus(T2DM)and its mechanism of action using transcriptome sequencing(RNA-seq).Methods C57BL/6J mice were randomly assigned to the control,T2DM,and T2DM+THC groups.After a high-fat meal and streptozotocin injection,the body weights and fasting blood glucose levels of each mouse with T2DM were measured.Hematoxylin and eosin staining,Oil red O staining,and RNA-seq were performed to examine kidney pathology,lipid deposition,and differentially expressed genes,respectively,in the mice.Results Mice in T2DM group exhibited significantly higher fasting blood glucose levels(P＜0.001),renal tubule degeneration,glomeruli enlargement,disordered epithelial cells,and increased kidney lipid deposition after 12 weeks compared with those of the control group.THC adminis-tration alleviated all these conditions(P＜0.001).RNA-seq analysis revealed significant gene expression variations among the control,T2DM,and T2DM+THC groups.THC may protect against T2DM-induced kidney injury and lipid deposition by regulating the cell cycle(apoptosis),P53 signaling pathway,and PPARγ signaling path way,as indicated by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.In mice with T2DM,THC intervention may upregulate the expression of Cd36,Lpl,PPARγ,and Plin4 genes in renal tissues,while downregulating Ccnb1,Ccnb2,Cdk1,Bub1,and Cdc25c gene expressions.The proteins encoded by the four upregulated genes interact,as do those encoded by the five downregulated genes.Conclusion THC administration improves fasting blood glucose levels,reduces renal damage,and decreases fat deposition in mice with T2DM.The processes may involve decreasing apoptosis,blocking the P53 signaling pathway,and activating the PPARγ signaling pathway.

Objective:To examine the manifestations and causes of administrative burden among primary healthcare professionals,and to explore its impact on job burnout through the mediating role of role conflict,providing theoretical and empirical support for governance-level burden-reduction strategies.Methods:An exploratory sequential mixed-methods design was employed,focusing on primary healthcare professionals in Shandong Province.In the first phase,in-depth interviews were conducted with 175 participants;in the second phase,a questionnaire survey of 1,096 participants and follow-up interviews with 107 participants were carried out.Results:The proportions of respondents who reported"heavy"or"very heavy"burdens were 62.7%for inspection,54.8%for documentation,51.8%for reporting,and 24.4%for meetings.Structural equation modeling showed that administrative burden had a direct effect on job burnout(0.150)and an indirect effect through role conflict(0.093).Qualitative findings further indicated that administrative burden largely stemmed from public health traceability requirements and medical insurance policies,and operated through both resource-based and value-based conflicts.Conclusions:Primary healthcare professionals face considerable administrative burdens,which may heighten job burnout through role conflict.Governance reforms should optimize inspection and assessment,streamline data reporting,refine record-keeping,and promote collaborative governance to break the chain of institutional pressure leading to burnout.

Objective To develop a toolkit suitable for assisting community health institutions in the early identification and inter-vention of mild cognitive impairment(MCI)among older adults.Methods A literature review was conducted to construct a draft of the identification and intervention toolkit.Tools with an expert approval rate above 70%were included after expert consultation.The final version of the toolkit was developed by integrating these tools with officially recommended tools in China.Results The expert consultation yielded an authority coefficient of 0.84.The finalized toolkit included the assessment tools of Mini-Mental State Examination,Montreal Cognitive Assessment,General Practitioner Assessment of Cognition,Cognitive Abilities Screening Instrument and Clock Drawing Test,and 18 intervention measures in-cluding pharmacological treatment,cognitive training and psychological interventions,etc.Conclusion The MCI Identification-Intervention Toolkit may serve as a reference for guiding the identification and inter-vention of MCI among older adults for community health institutions.

Objective To evaluate the safety and therapeutic efficacy of three-dimensional(3D)-printed personalized cervical correction pillows for treating cervical spondylotic radiculopathy.Methods A finite element model was established to simulate and analyze the biomechanical changes in cervical spine before and after using the pillow.Additionally,20 patients with chronic neck pain were included to analyze changes in visual analogue scale(VAS)scores,neck disability index(NDI),pressure pain threshold(PPT),Borden value,cervical lordosis,T1 slope,cervical slope,and thoracic inlet angle before and after using the pillow.Results Finite element analysis indicated that the maximum stress on vertebral bodies increased by 64.35％and the maximum stress on cartilage tissues by 5.09％after using the pillow.The Borden value improved by 45.75％.Clinical studies showed a significant reduction in VAS scores,NDI,and PPT after treatment(P＜0.05),while PPT,Borden value,cervical lordosis,T1 slope,and thoracic inlet angle significantly increased(P＜0.05).Conclusions The 3D-printed personalized cervical correction pillow is safe and effective in alleviating neck pain and improving cervical curvature,and it provides a new and effective non-surgical treatment option for cervical spondylotic radiculopathy,with significant clinical implications.