Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Objective:To systematically evaluate the fairness of traditional Chinese medicine (TCM) healthcare resource allocation at the prefecture-level in China using the healthcare resource agglomeration degree (HRAD) method, so as to provide empirical evidence for optimizing resource distribution.Methods:Data on TCM healthcare resources (including the number of TCM institutions, public TCM hospitals, TCM hospital beds, and TCM healthcare technicians) were collected from 333 prefecture-level regions in 2023. The HRAD method was employed to assess fairness in geographic allocation (HRAD i) and population-based allocation (HRAD i/PAD i). A multi-indicator comprehensive evaluation was conducted using the entropy weight method to determine weighting coefficients. Results:Significant disparities were observed in the geographic agglomeration of TCM resources (HRAD i) in China. Resource-rich regions (HRAD i>5) were primarily concentrated in eastern and some central-western provinces, while resource-scarce regions (HRAD i<1) were mainly distributed in western, northeastern, and parts of central and eastern provinces. Analysis of population-based fairness (HRAD i/PAD i) revealed that most prefecture-level cities nationwide had ratios<1, with only 8 provinces having more cities with ratios>1 than<1. The comprehensive evaluation showed that top-ranked cities in the east (e.g., Hangzhou, Dongying, Shenzhen), central region (e.g., Taiyuan, Zhengzhou), and west (e.g., Hainan Prefecture, Alxa League) were predominantly core cities or sparsely populated areas. Conclusions:China′s prefecture-level TCM healthcare resource allocation exhibits significant geographic and population-based inequities, with excessive concentration in provincial capitals and developed cities. Urgent strategies are needed to optimize resource allocation, enhance fairness and accessibility, including promoting the decentralization of high-quality resources, strengthening regional collaborative support, enhancing talent attraction in underdeveloped areas, and leveraging information technology to improve efficiency.

Removal of endogenic renal sinus tumors which are located at the renal hilum,is recognized as one of the most challenging surgeries in urology due to the complex anatomical structure.With the help of the high-definition field of vision and flexible robotic arms of the Da Vinci robot system,our team have carried out precision intra-sinus tumor enucleation based on preoperative interactive qualitative and Interactive Quantitative Quality Assurance for 3D Imaging(IQQA-3D)accurate reconstruction technology,as well as the clinical anatomical characteristics of patients with renal sinus tumors.During operation,the renal pedicle is fully dissected,the perihilar fat is cleared,and the tumor capsule is exposed.Subsequently,the blood supply to the kidney is blocked,and the tumor is precisely excised along the tumor capsule.The vascular stumps are sutured point-to-point,and the wound is closed and locked.After the blood supply restores,regional arterial occlusion is performed if necessary to ensure the safety of the surgery and maximize the preservation of renal function.This article discusses the definition of tumor boundaries during robot-assisted endogenic sinus tumor enucleation,the use of intraoperative cooling techniques,and the improvement of surgical safety.

Objective:To systematically evaluate the fairness of traditional Chinese medicine (TCM) healthcare resource allocation at the prefecture-level in China using the healthcare resource agglomeration degree (HRAD) method, so as to provide empirical evidence for optimizing resource distribution.Methods:Data on TCM healthcare resources (including the number of TCM institutions, public TCM hospitals, TCM hospital beds, and TCM healthcare technicians) were collected from 333 prefecture-level regions in 2023. The HRAD method was employed to assess fairness in geographic allocation (HRAD i) and population-based allocation (HRAD i/PAD i). A multi-indicator comprehensive evaluation was conducted using the entropy weight method to determine weighting coefficients. Results:Significant disparities were observed in the geographic agglomeration of TCM resources (HRAD i) in China. Resource-rich regions (HRAD i>5) were primarily concentrated in eastern and some central-western provinces, while resource-scarce regions (HRAD i<1) were mainly distributed in western, northeastern, and parts of central and eastern provinces. Analysis of population-based fairness (HRAD i/PAD i) revealed that most prefecture-level cities nationwide had ratios<1, with only 8 provinces having more cities with ratios>1 than<1. The comprehensive evaluation showed that top-ranked cities in the east (e.g., Hangzhou, Dongying, Shenzhen), central region (e.g., Taiyuan, Zhengzhou), and west (e.g., Hainan Prefecture, Alxa League) were predominantly core cities or sparsely populated areas. Conclusions:China′s prefecture-level TCM healthcare resource allocation exhibits significant geographic and population-based inequities, with excessive concentration in provincial capitals and developed cities. Urgent strategies are needed to optimize resource allocation, enhance fairness and accessibility, including promoting the decentralization of high-quality resources, strengthening regional collaborative support, enhancing talent attraction in underdeveloped areas, and leveraging information technology to improve efficiency.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objectives:To analyze the cardiac involvement of patients with Fabry disease(FD)in Anhui region.Methods:This retrospective analysis included 48 previously and currently diagnosed FD patients(25 males)in Anhui region,overall patient and gender specific cardiac involvement was analyzed.Results:The median age of FD patients is 28.0(19.0,46.0)years.The cardiac manifestations of patients with FD were most commonly characterized by palpitations/arrhythmias(13/42 cases)and exertional dyspnea(11/42 cases),electrocardiographic changes were most commonly characterized by T-wave inversion(22/42 cases),ST-segment depression(16/42 cases),and left ventricular hypervoltage(18/42 cases),cardiac structural and functional changes were most common in papillary muscle hypertrophy(29/36 cases),bilateral sign(22/37 cases)and left ventricular hypertrophy(21/46 cases),as well as reduced left ventricular global longitudinal strain(26/39 cases).Neuropathic pain(28/43 cases)was the most common extracardiac manifestation of FD patients.FD patients of different gender differed in age at diagnosis(P=0.018),alpha galactosidase A activity(P<0.001),globotriaosylsphingosine(lyso-GL3)levels(P<0.001),enzyme replacement therapy rate(P=0.043),dyshidrosis(P<0.01),and the incidence of angiokeratoma(P=0.004).Correlation analysis showed that genotype was not correlated with enzyme activity or Lyso-GL-3 levels,whereas the Sokolow-Lyon index was positively correlated with Lyso-GL-3 levels(ρ=0.423,P=0.008),and the Sokolow-Lyon indices(septal thickness:ρ=0.562,P<0.001;left ventricle posterior wall thickness:ρ=0.569,P<0.001)and QRS duration(septal thickness:ρ=0.543,P<0.001;left ventricle posterior wall thickness:ρ=0.557,P<0.001)were positively correlated with left ventricular wall thickness.Conclusions:Cardiac involvement in patients with FD in the Anhui region is characterised by palpitations or arrhythmias,accompanied by nonspecific electrocardiographic changes.Echocardiography frequently reveals papillary muscle hypertrophy.The manifestation of cardiac involvement in patients of different genders is similar.

Objective To observe the correlations of artificial intelligence(AI)measured parameters on anteroposterior and lateral spinal X-ray films with the severity of adolescent idiopathic scoliosis(AIS).Methods Totally 1 786 AIS patients were retrospectively enrolled.Parameters including Cobb angle(CA),coronal balance distance(CBD),T1 slope(T1S),pelvic tilt(PT),sacral slope(SS),apical vertebral translation(AVT),thoracic trunk shift(TTS),thoracic kyphosis(TK)and sagittal vertical axis(SVA)on anteroposterior and lateral spinal X-ray films were measured using uAI DR scoliosis analysis system.The severity of AIS was evaluated according to CA,and the correlations between other parameters and the severity of AIS were explored.The above parameters were compared under different severity levels and coronal/sagittal equilibrium states.Multivariate logistic regression analysis was performed to screen the independent impact factors on the severity of AIS.Results Significant differences of the above parameters were found among different severity levels except for SVA(all P＜0.001).With the aggravation of AIS,CA,CBD,AVT and TTS increased successively(all P＜0.001).T1S of severe AIS was higher than that of mild and moderate AIS(both P＜0.001),PT and SS of moderate and severe AIS were all bigger,while their TK were smaller than those of mild AIS(all P＜0.001).Significant differences of CA,T1S,PT,SS,AVT,TTS and TK were found between coronal balanced and imbalanced AIS(all P＜0.05),while of TK were found between sagittal balanced and unbalanced AIS(P=0.026).CBD,T1S,PT,SS,AVT and TTS were all positively correlated(r,=0.136-0.606,all P＜0.001),while TK was negatively correlated(r,=—0.404,P＜0.001)with the severity of AIS.T1S,AVT and TTS were all independent impact factors of the severity of AIS(all P＜0.001).Conclusion Among AI measured parameters on anteroposterior and lateral spinal X-ray films,CBD,T1S,PT,SS,AVT and TTS were positively correlated,while TK was negatively correlated with the severity of AIS.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To summarize clinical characteristics and prognosis of immune checkpoint inhibitor (ICI) -related Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) .Methods:A retrospective analysis was conducted on patients diagnosed with ICI-related SJS/TEN in Zhongda Hospital, Southeast University from January 2018 to October 2023. Data on clinical manifestations, laboratory examinations, treatment and prognosis of the patients were analyzed.Results:A total of 9 patients were diagnosed with ICI-related SJS/TEN, including 8 males and 1 female, with the onset age ranging from 58 to 77 (67.56 ± 7.33) years. ICI were applied to all the 9 patients before onset of SJS/TEN. The latent period was 6 - 261 d, and the median duration was 76 d. All the patients presented with erythema as initial lesions, 3 cases with target lesions, 6 with blisters, and 5 cases with a positive Nikolsky's sign. Oral mucosal damage occurred in 7 cases, eye damage occurred in 6 cases, and urogenital damage occurred in 6 cases. All the 9 cases were treated with systematic glucocorticoids, 7 cases with intravenous immunoglobulin and 7 cases with antibiotics. Eight cases recovered and 1 case died. Among 6 patients followed for an average of 6.92 months, none achieved complete or partial remission, 3 died and 3 experienced disease progression.Conclusions:ICI-related SJS/TEN occurred with a relatively long latent period, and all the cases presented with erythema initially, with mucosal damage present in most of the cases. Management required discontinuation of ICI, and most patients recovered with corticosteroids and intravenous immunoglobulin, however, the prognosis for the primary malignancy remained poor.

Objective:To analyze the relationship between neck pain severity and duration and cervical sagittal parameters in non-specific neck pain (NNP) patients from a real world data, and to initially explore the relationship between NNP and cervical sagittal position sequence.Methods:The clinical data of 126 patients with main complaint of neck pain in the outpatient department of Beijing Friendship Hospital, Capital Medical University from January to September 2023 were retrospectively analyzed. This cohort included 84 female and 42 male patients with a mean age of (42.21±14.88) years (aged from 15 to 76 years). According to the duration of neck pain was more than 3 month or not, patients were divided into acute neck pain group ( n=57) and chronic neck pain group ( n=69). Patients were divided into mild neck pain group ( n=72) and moderate and severe neck pain group ( n=54) according to the severity of neck pain. The duration and visual analogue scale (VAS) of neck pain for each patient was recorded. Cervical sagittal related parameters, including cervical lordosis (C 2-C 7 Cobb′ angle, CL), C 2-C 7 sagittal vertical axis (cSVA), T 1 slope (TS) were measured by cervical lateral X-ray, and the value of T 1 slope minus cervical lordosis (TS-CL) was calculated. At the same time, cervical lateral X-ray was used to record whether the patient had cervical kyphosis and whether the patient was associated with ossification of the nuchal ligament (ONL). The VAS score of neck pain was expressed as the median (interquartile) [ M( Q1, Q3)]. Measurement data with normal distribution were represented as mean±standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data were represented as cases and percentage, and was conducted by Chi-square test. Spearman correlation analysis was used to investigate the correlation of VAS score and duration of neck pain with age, gender, imaging parameters (CL, cSVA, TS, TS-CL), cervical kyphosis and ONL. Results:The median VAS score of all patients with neck pain was 4(3, 5). For all patients, VAS score of neck pain was significantly correlated with cSVA ( P=0.029) and TS-CL ( P=0.028). There was no correlation between VAS score and CL ( P=0.235), TS ( P=0.355), with cervical kyphosis or not ( P=0.988), or with ONL or not ( P=0.181). The TS-CL values of acute neck pain group and chronic neck pain group were (11.80±8.38)° and (8.77±7.61)°, respectively, with a significant difference ( P=0.035). There was no significant difference in the incidence of cSVA, CL, TS, ONL and cervical kyphosis between the two groups ( P>0.05). The cSVA of mild neck pain group and moderate and severe neck pain group were (1.16±0.94) cm and (1.80±1.04) cm, respectively. CL was (12.25±10.76)° and (8.27±9.08)°, respectively. The TS-CL values were (8.11±7.54)° and (12.84±8.04)°, respectively, and the differences between the two groups were statistically significant ( P<0.05). The incidence of ONL in moderate and severe neck pain group was significantly higher (35.2% vs 19.4%), and the difference was statistically significant ( P<0.05). Conclusions:The severity of NNP was significantly correlated with cSVA, the more severe the neck pain, the more the mismatch between TS and CL was presented. Compared with chronic neck pain, patients with acute neck pain tended to appear TS and CL mismatch. There was a large value of cSVA and TS-CL in moderate and severe neck pain patients. The incidence of ONL was significantly increased in patients with moderate and severe neck pain.