OBJECTIVE To investigate the establishment and promotion of a new standardized management model for anti- osteoporosis medication after fragility fracture surgery by resident clinical pharmacists， and provide references for resident pharmacists to carry out clinical pharmaceutical services. METHODS From July 2023 to March 2024，595 post-brittle fracture surgery patients were enrolled. Using the PDCA （plan-do-check-act） cycle，resident clinical pharmacists identified issues and conducted investigations in clinical practice. Through integrating clinical pharmacist intervention services before， during and after treatment， a medication treatment pathway was developed， thereby establishing a standardized management model for anti- osteoporosis treatment following fragility fracture surgery. Leveraging the National Brittle Fracture Big Data Platform （under the National Clinical Research Center for Orthopedics and Sports Rehabilitation）， a dedicated data module was constructed， providing big data support to evaluate the efficacy of this pharmaceutical care model. RESULTS Continuous PDCA cycle driven improvements significantly increased the proportion of osteoporosis diagnosis （from 9% before intervention to 81%） and proportion of drug treatment （from 4% to 75%）.The proportions of bone density and bone metabolism testing also rose markedly，positively impacting long-term patient outcomes. CONCLUSIONS The establishment of a standardized management model for anti- osteoporosis treatment following fragility fracture surgery by resident clinical pharmacists has enhanced clinicians’ diagnostic and therapeutic capabilities for osteoporosis， ensures rational medication use in osteoporosis patients， and demonstrates significant potential for widespread adoption and application.

OBJECTIVE: To evaluate the safety and effectiveness of anterior cervical discectomy and fusion (ACDF) by using zero-profile anchored cage (ZAC) in treatment of consecutive three-level cervical spondylosis, by comparing with plate-cage construct (PCC). METHODS: A clinical data of 65 patients with cervical spondylosis admitted between January 2020 and December 2022 and met the selection criteria was retrospectively analyzed. During consecutive three-level ACDF, 35 patients were fixed with ZAC (ZAC group) and 30 patients with PCC (PCC group). There was no significant difference in baseline data between the two groups ( P>0.05), including gender, age, body mass index, surgical segment, preoperative Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), visual analogue scale (VAS) score, prevertebral soft tissue thickness (PSTT), cervical lordosis, and surgical segmental angle. The operation time, intraoperative blood loss, hospital stay, clinical indicators (JOA score, NDI, VAS score), and radiological indicators (cervical lordosis, surgical segmental angle, implant subsidence, surgical segment fusion, and adjacent segment degeneration), and the postoperative complications [swelling of the neck (PSTT), dysphagia] were recorded and compared between the two groups. RESULTS: Patients in both groups were followed up 24-39 months. There was no significant difference in follow-up duration between the two groups ( P>0.05). The operation time and intraoperative blood loss were lower in ZAC group than in PCC group, and the length of hospital stay was longer, but there was no significant difference ( P>0.05). At each time point after operation, both groups showed significant improvements in JOA score, VAS score, and NDI compared with preoperative scores ( P<0.05), but there was no significant difference between the two groups at each time point after operation ( P>0.05). Both groups showed an increase in PSTT at 3 days and 3, 6 months after operation compared to preoperative levels ( P<0.05), but returned to preoperative levels at last follow-up ( P>0.05). The PSTT at 3 days and 3 months after operation were significantly lower in ZAC group than in PCC group ( P<0.05), and there was no significant difference between the two groups at 6 months and at last follow-up ( P>0.05). The incidences of dysphagia at 3 days and 3 months were significantly lower in ZAC group than in PCC group ( P<0.05), while no significant difference was observed at 6 months and last follow-up between the two groups ( P>0.05). There was no postoperative complication in both groups including hoarseness, esophageal injury, cough, or hematoma. Both groups showed improvement in cervical lordosis and surgical segmental angle compared to preoperative levels, with a trend of loss during follow-up. The cervical lordosis loss and surgical segmental angle loss were significantly more in the ZAC group than in PCC group ( P<0.05). The incidence of implante subsidence was significantly higher in ZAC group than in PCC group ( P<0.05). There was no significant difference between the ZAC group and PCC group in the incidences of surgical segment fusion and adjacent segment degeneration ( P>0.05). CONCLUSION In consecutive three-level ACDF, both ZAC and PCC can achieve satisfactory effectiveness. The former can reduce the incidence of postoperative dysphagia, while the latter can better maintain cervical curvature and reduce the incidence of implant subsidence.
Humans ; Spondylosis/surgery* ; Cervical Vertebrae/surgery* ; Spinal Fusion/instrumentation* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Diskectomy/instrumentation* ; Bone Plates ; Treatment Outcome ; Adult ; Aged ; Internal Fixators ; Operative Time ; Length of Stay

OBJECTIVE: To investigate the mechanism of electroacupuncture (EA) in treating diabetic gastroparesis (DGP) by inhibiting the activation of Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome and pyroptosis mediated via NLRP3/cysteinyl aspartate specific proteinase-1 (caspase-1)/gasdermin D (GSDMD) signaling pathway. METHODS: Forty Sprague-Dawley rats were randomly divided into 4 groups including the control, DGP model, EA, and MCC950 groups. The DGP model was established by a one-time high-dose intraperitoneal injection of 2% streptozotocin and a high-glucose and high-fat diet for 8 weeks. EA intervention was conducted at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) with sparse-dense wave for 15 min, and was administered for 3 courses of 5 days. After intervention, the blood glucose, urine glucose, gastric emptying, and intestinal propulsive rate were observed. Besides, HE staining was used to observe histopathological changes in gastric antrum tissues, and TUNEL staining was utilized to detect DNA damage. Protein expression levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, caspase-1 and GSDMD were measured by Western blot. Immunofluorescence staining was employed to assess the activity of GSDMD-N. Lactate dehydrogenase (LDH) levels were detected by using a biochemical kit. RESULTS: DGP rats showed persistent hyperglycemia and a significant decrease in gastrointestinal motility (P<0.05 or P<0.01), accompanied by pathological damage in their gastric antrum tissues. Cellular DNA was obviously damaged, and the expressions of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD proteins were significantly elevated, along with enhanced fluorescence signals of GSDMD-N and increased LDH release (P<0.01). EA mitigated hyperglycemia, improved gastrointestinal motility in DGP rats and alleviated their pathological injury (P<0.05). Furthermore, EA reduced cellular DNA damage, lowered the protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD, suppressed GSDMD-N activity, and decreased LDH release (P<0.05 or P<0.01), demonstrating effects comparable to MCC950. CONCLUSION EA promotes gastrointestinal motility and repairs the pathological damage in DGP rats, and its mechanism may be related to the inhibition of NLRP3 inflammasome and pyroptosis mediated by NLRP3/caspase-1/GSDMD pathway.
Animals ; Electroacupuncture ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Pyroptosis ; Rats, Sprague-Dawley ; Caspase 1/metabolism* ; Gastroparesis/physiopathology* ; Signal Transduction ; Male ; Diabetes Mellitus, Experimental/physiopathology* ; Phosphate-Binding Proteins/metabolism* ; Gastrointestinal Motility ; Rats ; Intracellular Signaling Peptides and Proteins/metabolism* ; Diabetes Complications/physiopathology* ; Gasdermins

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is an adaptive immune system present in most bacteria and archaea, protecting them from infection by exogenous genetic elements. Due to its simplicity, cost-effectiveness, and precise gene editing capabilities, CRISPR/Cas technology has emerged as a promising tool for treating diseases. The continuous refinement of derivative systems has further broadened its scope in disease treatment. Nevertheless, the heterogeneous physiopathological nature of diseases and variations in disease onset sites pose significant challenges for in vivo applications of CRISPR systems. The efficiency of CRISPR systems in disease treatment is directly influenced by the performance of the delivery system. Additionally, concerns such as off-target effects present crucial hurdles in the clinical implementation of CRISPR systems. This review provides a comprehensive overview of the development of CRISPR systems, vector technologies, and their applications in disease treatment, while also addressing the challenges encountered in clinical settings. Furthermore, future research directions are outlined to pave the way for advancements in CRISPR-based therapies.

OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

Objective To evaluate the value of a nomogram model based on ultrasonographic features and inflammatory indicators in the preoperative noninvasive prediction of pathological grading of urothelial carcinoma of bladder(UCB).Methods A retrospective analysis was conducted on 471 patients with pathologically confirmed UCB,and the patients were assigned to high-grade group(401 cases)or low-grade group(70 cases).Basic clinical data(gender,age,macroscopic hematuria),ultrasonographic features(lesion location,blood flow signal,etc.),and blood inflammatory indicators(e.g.neutrophil-to-lymphocyte ratio[NLR])were collected.Independent predictors were screened using univariate and multivariate logistic regression,and a nomogram model was constructed.Model performance was evaluated using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Multivariate logistic analysis identified gender(odds ratio[OR]=2.68),age(OR=1.08),macroscopic hematuria(OR=3.19),lesion located in the trigone(OR=4.59),positive blood flow signal(OR=2.87),and NLR(OR=1.03)were independent predictors of high-grade UCB(all P＜0.05).The combined model(clinical features+ultrasonographic characteristics+inflammatory indicators)achieved an area under curve(AUC)of 0.892,which was significantly higher than the clinical feature-only model(AUC=0.799)and the clinical+ultrasonographic model(AUC=0.856).The calibration curve demonstrated good consistency between predicted and actual outcomes,and DCA confirmed its optimal clinical net benefit.Conclusion The nomogram model integrating clinical features,ultrasonographic characteristics,and inflammatory indicators can effectively discriminate UCB pathological grading,providing a reliable preoperative noninvasive assessment tool for personalized treatment decisions.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective To assess the effectiveness of the evaluation of military physical function(EMPF)system in predicting the occurrence of military training injuries among new recruits to provide scientific guidance and methodological choice for military training.Methods A total of 527 new recruits from 5 grassroots units from July 2016 to February 2018 were selected for the study.The recruits underwent EMPF testing,and their military training injuries were monitored over a 2-year follow-up period.Those who sustained injuries during training were divided into injury group(n=163),while the remaining recruits were placed in healthy group(n=364).The predictive ability of the total EMPF score for training injuries was assessed using the receiver operating characteristic curve(ROC),and the correlation between the total EMPF score,individual test scores,and military training injuries were analyzed using binary logistic regression.Results The total EMPF score of new recruits in injury group(19.52±1.97)was significantly lower than that of healthy group(24.31±1.54)(P<0.001),which also demonstrated a high diagnostic value in predicting the risk of military training injuries,with an area under the curve(AUC)of ROC of 0.971(P<0.001).A cut-off value of 22 scores was found to have the highest accuracy in predicting future training injuries,with an odds ratio(OR)of 25.63,sensitivity of 0.939,specificity of 0.879,positive likelihood ratio of 7.76,and a post-test probability of 0.67.Binary logistic regression analysis revealed that 6 EMPF tests,including holding the ball over and leaning back,bending forward and touching the ground with the ball,lunge squat and twist,swallow balance with holding the ball afterward,vertical jump,and respiratory pattern assessment,were negatively associated with the risk of military training injuries(P<0.0001).Conclusion The EMPF system can effectively predict the risk of military training injuries,with military personnel whose total EMPF score is less than 22 being at higher risk of sustaining such injuries.