BACKGROUND:Primary osteoporosis has a high incidence,but the pathogenesis is not fully understood.Currently,there is a lack of effective early screening indicators and treatment programs. OBJECTIVE:To further explore the mechanism of primary osteoporosis through comprehensive bioinformatics analysis. METHODS:The primary osteoporosis data were obtained from the gene expression omnibus(GEO)database,and the differentially expressed genes were screened for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.In addition,the differentially expressed genes were subjected to protein-protein interaction network to determine the core genes related to primary osteoporosis,and the least absolute shrinkage and selection operator algorithm was used to identify and verify the primary osteoporosis-related biomarkers.Immune cell correlation analysis,gene enrichment analysis and drug target network analysis were performed.Finally,the biomarkers were validated using qPCR assay. RESULTS AND CONCLUSION:A total of 126 differentially expressed genes and 5 biomarkers including prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,transforming growth factor B1,and retinoblastoma gene 1 were obtained in this study.GO analysis showed that differentially expressed genes were mainly concentrated in the cellular response to oxidative stress and the regulation of autophagy.KEGG analysis showed that autophagy and senescence pathways were mainly involved.Immunoassay of biomarkers showed that prostaglandins,retinoblastoma gene 1,and mitogen-activated protein kinase 3 were closely related to immune cells.Gene enrichment analysis showed that biomarkers were associated with immune-related pathways.Drug target network analysis showed that the five biomarkers were associated with primary osteoporosis drugs.The results of qPCR showed that the expression of prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,and transforming growth factor B1 in the primary osteoporosis sample was significantly increased compared with the control sample(P<0.001),while the expression of retinoblastoma gene 1 in the primary osteoporosis sample was significantly decreased compared with the control sample(P<0.001).Overall,the study screened and validated five potential biomarkers of primary osteoporosis,providing a reference basis for further in-depth investigation of the pathogenesis,early screening and diagnosis,and targeted treatment of primary osteoporosis.

Idiopathic oligoasthenospermia （IO） has been increasingly emphasized in the diagnosis and treatment of male infertility. Oxidative stress damage directly affects sperm quality and spermatogenesis， constituting a major causative factor of IO. Firstly， due to its high content of polyunsaturated fatty acids， the sperm plasma membrane is highly sensitive to reactive oxygen species （ROS）， leading to lipid peroxidation accumulation and even inducing ferroptosis. Secondly， deficient downstream key proteins in the base excision repair pathway render sperm unable to repair extensive DNA oxidative damage under oxidative stress. Simultaneously， under oxidative stress， the apoptotic pathway of sperm is cascade-activated， causing rapid loss of motility. ROS further disrupts the hypothalamic-pituitary-gonadal axis， inhibiting testosterone production and ultimately affecting spermatogenesis. Wuzi Yanzongwan，in line with traditional Chinese medicine theory of treating IO through "nourishing kidney essence and harmonizing Yin and Yang"， clinically demonstrates its ability to improve sperm morphology， count， and motility， thereby enhancing male fertility. The research on the pharmacological constituents of Wuzi Yanzongwan primarily involves establishing a characteristic spectrum of Chinese medicine to achieve quality control and exploring the pharmacology of effective components. Studies have found that its main active ingredients consist of flavonoids and phenylpropanoids. Specifically， compounds such as hyperin， acteoside， kaempferol， and schisandrin A are identified as the primary active substances and quality control components. These compounds exhibit strong antioxidant activity and have been partly applied in research related to reproductive endocrine disorders. Tripterygium glycoside is primarily used for modeling of oxidative stress-induced IO. It leads to the accumulation of various lipid peroxides in testicular tissues and concurrently compromises the body's antioxidant capacity. Mechanistic studies have found that Wuzi Yanzongwan can inhibit elevated ROS levels in IO models and enhance the body's antioxidant capacity， thereby ameliorating inflammation， suppressing cell apoptosis， promoting testosterone production， and ultimately alleviating the decline in sperm quality and spermatogenesis caused by oxidative stress.

Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.

Objective:To explore the clinical outcomes of locking compression plating (LCP) in the treatment of periprosthetic fracture (PPF) of the distal femur in the aged patients.Methods:A retrospective study was performed to analyze the 31 aged patients who had been treated at Department of Orthopedic Surgery, The Affiliated Hospital to Nantong University for PPF of the distal femur with LCP between June 2012 and May 2023. There were 27 females and 4 males with an age of (80.2±6.1) years. According to the Unified Classification System (UCS), 18 PPFs were classified as type Ⅴ.3B1 and 6 PPFs as type Ⅴ.3B2 after total knee arthroplasty and 7 PPFs as type Ⅳ.3C after total hip arthroplasty. The patients were fixated with a lateral single plate in 25 cases, and with lateral and medial dual plates in 6 cases. The surgical time, intraoperative blood loss, hospitalization time, postoperative weight-bearing time, fracture healing time, and knee joint function and complications during follow-up were recorded.Results:For the 25 patients undergoing fixation with a lateral single plate, the surgical time was (58.7±7.9) minutes, the intraoperative blood loss (78.0±15.1) mL, the hospitalization time (6.9±1.6) days, the postoperative weight-bearing time (5.9±1.4) days, and the follow-up time 37 (15, 51) months. For the 6 patients undergoing fixation with lateral and medial dual plates, the surgical time was (186.6±9.8) minutes, the intraoperative blood loss (1,256.7±231.2) mL, the hospitalization time (17.8±3.3) days, the postoperative weight-bearing time (3.6±0.6) days, and the follow-up time 17 (16, 21) months. The fracture healing time was (14.9±2.0) and (18.7±2.6) weeks, respectively, for patients fixed with single and double steel plates. By the scoring criteria of the American Hospital for Special Surgery (HSS), the knee joint function was evaluated at the last follow-up as excellent in 10 cases and as good in 15 cases for the 25 patients undergoing fixation with a lateral single plate, and as good for all the 6 patients undergoing fixation with lateral and medial dual plates. No patient experienced such complications as incision infection, bone nonunion, or internal fixation failure during the follow-up period.Conclusions:LCP fixation can achieve satisfactory outcomes in the treatment of PPF of the distal femur in the aged patients. As fixation with a single lateral femoral plate is suitable for most of the aged patients with PPF of the distal femur, it can be used as the first choice. Fixation with dual plates can provide stronger stability, but its indications should be strictly controlled.

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. Conclusions Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4⁺Tnni1⁺ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.
Animals ; Mice ; Diploidy ; Heart ; Myocytes, Cardiac/metabolism* ; Cell Communication ; Gene Expression Profiling ; Mitochondria ; Regeneration ; Mammals/genetics*

ObjectiveTo evaluate the efficacy of Geriatric Nutritional Risk Index (GNRI) on admission on predicting neurological outcomes for stroke patients at the convalescence stage (three months after stroke). MethodsA total of 277 inpatients with ischemic stroke in Wenzhou TCM Hospital of Zhejiang Chinese Medical University from November, 2022 to January, 2023 were divided into good outcome group (n = 195) and poor outcome group (n = 82) according to the score of modified Rankin Scale (mRS) three months after stroke. Their clinical data and GNRI were compared. ResultsCompared with the good outcome group, the poor outcome group showed a lower level of GNRI (t = -9.569, P < 0.001), more proportion of patients with high nutritional risk (χ² = 68.861, P < 0.001). More cases with poor outcome were found with higher nutritional risk (Z = 65.406, P < 0.001). After covariate adjustment, higher level of GNRI was an independent protective factor for poor outcome three months after stroke (OR = 0.895, 95%CI 0.864 to 0.927, P < 0.05), and the OR increased with the nutritional risk grade of GNRI (P < 0.05). The area under the curve (AUC) of GNRI, score of NIHSS, and BMI were 0.812 (Z = 11.576, P < 0.001), 0.759 (Z = 8.328, P < 0.001), and 0.594 (Z = 2.716, P = 0.007), respectively; while the combination of GNRI and NIHSS was more effective (AUC = 0.875, Z = 17.389, P < 0.001). The sensitivities of GNRI, NIHSS and the combination of the two in predicting neurological function were 65.85%, 76.83% and 79.21%, respectively, and the specificities were 81.54%, 60.51% and 82.95%, respectively. ConclusionGNRI on admission is associated with neurological function three months after stroke. GNRI can be used alone or in combination with NIHSS score to predict neurological outcome in the rehabilitation period, which is a useful complement to traditional predictors.

Objective:To investigate the surgical method of LC-II screws for fragility fractures of the pelvis (FFP) in the elderly and evaluate its clinical efficacy.Methods:A retrospective analysis was performed on 45 patients with FFPs operated in our department from January 2011 to January 2022. The clinical information was as follows. The FFP classification of pelvic fracture was IIIA in 26 cases and IIIB in 19 cases. Among them, 22 cases were fixed with closed reduction and modified LC-II screws (experimental group), and 23 cases were fixed with open reduction and reconstruction plates (control group). In the experimental group, there were 6 males and 16 females. The age range was 62-90 years, with an average of 73.2±9.2 years. The FFP classification of pelvic fracture was IIIA in 12 cases and IIIB in 10 cases. In the control group, there were 8 males and 15 females. The age range was 60-87 years, with an average of 72.8±6.6 years. FFP classification of pelvic fracture was IIIA in 14 cases and IIIB in 9 cases. After admission, pelvic X-ray and CT scan were performed, and the surgery was prepared. In the experimental group, after closed reduction of the posterior ring, the modified LC-II screw was inserted below the anterior inferior iliac spine (AIIS) toward the sacroiliac joint and penetrated the sacroiliac joint. For combined anterior ring fractures, the INFIX was used for anterior ring fixation. In the control group, the posterior ring was fixed with a reconstruction plate and/or sacroiliac screw after open reduction through the lateral rectus approach (LRA). The clinical efficacy was evaluated between the experimental group and the control group.Results:All 45 patients were successfully operated and followed up for 6 months to 3 years. All the pelvic fractures healed. In the experimental group of 22 cases, the time from injury to operation was 3-9 days, with an average of 5.8±1.9 days; the operation time was 25-70 min, with an average of 42.0±12.9 min. The intraoperative bleeding was 20-40 ml, with an average of 29.1±6.7 ml. According to the X-ray reduction evaluation criteria of Matta, 7 cases were excellent, 11 cases were good and 4 cases were medium, with an excellent and good rate of 81.8%. According to rehabilitation criteria of Majeed, 10 cases were excellent, 6 cases were good and 6 cases were fair, with a total excellent and good rate of 72.7%. At the last follow-up, sacroiliac joint pain was evaluated by VAS score: 0 in 10 cases, <3 in 7 cases, and 4-6 in 5 cases. No internal fixation loosening occurred. In the control group, the time from injury to operation was 5-20 days, with an average of 9.9±3.8 days; the operation time was 50-150 min, with an average of 89.1±29.5 min; the intraoperative bleeding was 220-1 000 ml, with an average of 509.2±214.3 ml. According to the X-ray reduction evaluation criteria of Matta, 16 cases were excellent, 4 cases were good and 3 cases was medium, with an excellent and good rate of 87.0%. According to rehabilitation criteria of Majeed, 12 cases were excellent, 6 cases were good and 7 cases were fair, with a total excellent and good rate of 78.3%. At the last follow-up, sacroiliac joint pain was evaluated by VAS score: 0 in 14 cases, <3 in 6 cases, and 4-6 in 3 cases. In the control group, posterior ring plate loosening was found in 2 cases and anterior ring pubic ramus plate and screw loosening was found in 4 cases, but there was no reduction loss.Conclusion:The modified LC-II screw is theoretically feasible in the treatment of FFP. Preliminary clinical results show good safety and efficacy, providing a new idea for minimally invasive treatment of FFP.

Objective:To explore the clinical characteristics of pneumocystis carinii pneumonia (PCP) after kidney transplantation.Methods:From January 2020 to January 2022, clinical data were retrospectively reviewed for 13 renal transplant recipients with pneumocystis pneumonia diagnosed by metagenomics next generation sequencing (mNGS). There were 3 females and 10 males with an age range of (46±10) years.The median time of postoperative onset was 10(2-21) months; The major clinical manifestations included fever ( n=11), cough ( n=7), expectoration ( n=6) and dyspnea ( n=11). Paired t-test was employed for analyzing the laboratory results at admission and discharge. Results:The diagnosis was confirmed by the detection of NGS in alveolar lavage fluid or venous blood.The levels of G test, LDH test, total T lymphocyte absolute count (CD3+ Abs), inhibitory/cytotoxic T lymphocyte count (CD3+ CD8+ Abs) and auxiliary/induced T lymphocyte absolute count (CD3+ CD4+ Abs) were (543.27±440.49) pg/ml, (529.98±222.43)U/L and (191.92±119.42)/μl, (87.33±50.59)/μl and (106.92±87.42)/μl at admission and (69.58±50.21) pg/ml, (285.38±46.62 U/L), (888.58±672.99)/μl, (336.83±305.21)/μl and (520.08±388.76)/μl at discharge.The differences were statistically significant ( P<0.001, P=0.002, 0.006, 0.017, 0.005). All of them received compound sulfamethoxazole and caspofungin.Except for one death due to septic shock after 21-day treatment, 12 cases were cured. Conclusions:mNGS test is one of the important tool for an early diagnosis of PCP.Combined use of compound sulfamethoxazole and caspofungin is an effective anti-infective regimen.And immune function monitoring is vital for adjusting antibiotic and immunosuppressive regimens.

Objective:To investigate the effects of body mass index (BMI) levels at different baseline on the risk of new-onset acute pancreatitis (AP).Methods:The subjects were from the Kailuan Study Cohort and divided into 3 groups according to baseline BMI levels: BMI<24 kg/m 2, normal weight; BMI 24-28 kg/m 2, overweight; BMI≥28 kg/m 2, obesity. The incidence of new-onset AP in these three groups was analyzed. The survival curve was plotted by Kaplan-Meier method, the cumulative incidence was calculated and tested by log-rank method. Multivariate Cox proportional hazards regression model was used to calculate HR of baseline BMI levels for AP. Results:A total of 123 841 subjects were included and followed up for (11.94±2.13) years, during which, 395 cases were found with AP. The incidence of AP was 2.67 per 10 000 person years in total population, and the incidences of AP were 2.20, 2.72 and 3.58 per 10 000 person-years in the normal, overweight and obesity groups, respectively. The cumulative incidences of AP was 0.32%, 0.40% and 0.49% in normal, overweight and obesity groups, respectively, which showed a significant inter-group difference by log-rank test ( χ2=13.17, P<0.01). The results of multivariable adjusted Cox proportional hazards regression model analysis indicated that obesity group ( HR=1.45, 95% CI: 1.10-1.92) had a higher risk for AP compared with the normal BMI group. The subgroup analyses by age and sex showed that compared with the normal weight group,the HRs for AP in the obesity group was 1.58(95% CI:1.14-2.19) and 1.40(95% CI:1.03-1.90) among subjects younger than 60 years old and male subjects, respectively. After excluded onset AP within two years from baseline,with a control group from normal weight,the results of multivariate Cox proportional hazards regression model analysis indicated that the AP in the obesity group was 1.60 (95% CI: 1.18-2.15). Conclusion:Obesity may increase the risk of developing AP, particularly among young and middle-aged men.