This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

This study investigated the mechanism of Croci Stigma in treating immune checkpoint inhibitor(ICI)-associated myocarditis based on network pharmacology and molecular docking. Network pharmacology was employed to screen the active ingredients and molecular targets of Croci Stigma in treating ICI-associated myocarditis. The "drug-ingredient-target-disease" network and protein-protein interaction network were constructed to screen the key ingredients and core targets. Gene Ontology functional enrichment analysis showed that the mechanism was related to the regulation of inflammation and apoptosis. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the treatment was related to the advanced glycation end product-receptor for advanced glycation end products(AGE-RAGE) signaling pathway. Molecular docking result showed that crocins had close associations with RAC-alpha serine/threonine-protein kinase 1(AKT1), signal transducer and activator of transcription 3, and matrix metalloproteinase 9. Crocins were then selected as the therapeutic drug. The mouse model of ICI-associated myocarditis was established by subcutaneous injection of porcine cardiac myosin combined with intraperitoneal injection of pembrolizumab. The results suggested that Croci Stigma reduced the spleen index but had no effect on the heart index. The electrocardiogram showed that Croci Stigma increased the heart rate and shortened PR and QRS intervals. Echocardiographic data indicated that Croci Stigma increased the left ventricular stroke volume, cardiac output, ejection fraction, and fractional shortening. Hematoxylin-eosin and Masson staining results showed that Croci Stigma decreased the number of inflammatory cells infiltrating in the myocardium and alleviated myocardial fibrosis. Enzyme-linked immunosorbent assay results showed that Croci Stigma decreased the serum levels of inflammatory cytokines including tumor necrosis factor-alpha, interleukin-6, interleukin-12, and regulated on activation, normal T-cell expressed and secreted and lowered the levels of creatine kinase and creatine kinase isoenzyme MB. Biochemical data suggested that Croci Stigma inhibited the activities of superoxide dismutase and lactate dehydrogenase. Western blot result showed that Croci Stigma regulated the expression of myocardial AKT. The findings demonstrate that Croci Stigma may regulate AKT expression to effectively protect the cardiac tissue from ICI-associated myocarditis through antagonizing immune responses and inflammation, inhibiting oxidative stress, alleviating cardiac fibrosis, relieving cardiac block, and improving the cardiac function.
Animals ; Molecular Docking Simulation ; Myocarditis/metabolism* ; Immune Checkpoint Inhibitors/adverse effects* ; Mice ; Network Pharmacology ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Humans ; Protein Interaction Maps/drug effects*

PURPOSE: Bone cement-reinforced fenestrated pedicle screws (FPSs) have been widely used in the internal fixation and repair of the spine with osteoporosis in recent years and show significant improvement in fixation strength and stability. However, compared with conventional reinforcement methods, the advantages of bone cement-reinforced FPSs remain undetermined. This article compares the effects of fenestrated and conventional pedicle screws (CPSs) combined with bone cement in the treatment of osteoporosis. METHODS: A clinical control study of FPSs and CPSs combined with bone cement reinforcement in osteoporotic vertebral internal fixation was performed using the database PubMed, Embase, Cochrane Library, CNKI, the Wanfang, and the China Biomedical Literature Service System. Two evaluators screened the relevant literature in strict accordance with the inclusion criteria (diagnosis of participants, type of clinical study, treatment with FPS and CPS, and outcome indicators) and exclusion criteria (duplicate literature and missing or incorrect data) and independently conducted data extraction and quality evaluation. Clinical control studies of direct comparison between FPS and CPS combined with bone cement reinforcement in patients who were definitively diagnosed with thoracolumbar fractures or spinal degenerative diseases were included. Quality evaluation was conducted using the Cochrane risk bias evaluation tool for randomized controlled studies and using the Newcastle-Ottawa scale for retrospective case-control studies. RevMan software (version 5.3) was used for the meta-analysis to compare the clinical efficacy, radiological results, and related complications of the 2 methods. RESULTS: A total of 13 articles were included, including 7 randomized controlled studies and 6 retrospective case-control studies. There were 909 patients in these studies, 451 in the FPS and polymethyl methacrylate (FPS & PMMA) group and 458 in the CPS and polymethyl methacrylate (CPS & PMMA) group. The results of the meta-analysis showed that there was no significant difference between the 2 groups in operation time, hospital stay, visual analogue score, Japanese orthopaedic association score, Oswestry disability index score, Cobb angle, vertebral body deformation index and fusion rate (p > 0.05). The mean difference of intraoperative bleeding volume was -10.45, (95% confidence intervals (CI) (-16.92, -3.98), p = 0.002), the mean difference of loss height of the anterior edge of the vertebral body after surgery was -0.69 (95% CI (-0.93, -0.44), p < 0.001), and the relative risk (RR) of overall complication rate was 0.43 (95% CI (0.27, 0.68), p < 0.001), including the RR of bone cement leakage rate was 0.57 (95% CI (0.39, 0.85), p = 0.005). The screw loosening rate (RR = 0.26, 95% CI (0.13, 0.54), p < 0.001) of the FPS group was significantly lower than that of the CPS group. CONCLUSION The existing clinical evidence shows that compared with the CPS combined with bone cement, the use of FPS repair in the internal fixation of an osteoporotic vertebral body can reduce the amount of intraoperative bleeding, be more conducive to maintaining the height of the vertebral body, and significantly reduce the incidence of postoperative complications such as bone cement leakage and screw loosening.
Humans ; Pedicle Screws ; Bone Cements ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Fracture Fixation, Internal/instrumentation*

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

OBJECTIVE: To explore a predictive model that can better predict the prognosis of patients with diffuse large B-cell lymphoma (DLBCL), and validate its clinical value. METHODS: Clinical data of 134 newly treated DLBCL patients were collected from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2015 to January 2020. Several risk factors of the patients were screened and analyzed, a novel prognostic model were then established based on this, and its clinical application potential was validated. RESULTS: In the novel model, predicting progression-free survival (PFS) based on the age at initial treatment, albumin level, Hans classification, Ann Arbor stage, and BCL2 expression showed better predictive performance than International Prognostic Index (IPI) score (AUC: 0.788 vs 0.620，P <0.001). Predicting overall survival (OS) based on the age at initial treatment, albumin level, lactate dehydrogenase (LDH) level, and expressions of BCL2 and MUM1 proteins also showed better predictive performance for mortality risk than IPI score (AUC: 0.817 vs 0.624，P <0.001). CONCLUSION This novel prognostic model can better predict the survival prognosis of DLBCL patients compared to the IPI scoring system.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Risk Factors ; Male ; Female ; Middle Aged

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Langerhans cell histiocytosis of bone is a rare tumor disease characterized by the large accumulation of CD1a⁺ and CD207⁺ dendritic cells in tissues of unknown cause.It mainly occurs in children aged 1-4 years old,with incidences of 4-6 per million in children and 1-2 per million in adults.Due to its low incidence,diverse clinical manifestations,and no obvious specificity of imaging manifestations,the definitive diagnosis and early treatment of this type of tumor are challenging.In this paper,we report 8 cases of Langerhans cell histiocytosis of bone and review the relevant literature published in the past five years to summarize the clinical characteristics,pathological features,diagnosis,treatment,and prognosis of this disease.
Humans ; Bone Diseases/therapy* ; Histiocytosis, Langerhans-Cell/therapy*

Background The power industry is characterized by typical shift work systems, with 24-hour uninterrupted work demands, high intensity and high standard job characteristics, as well as emergent task pressure, which exposes employees to the long-term dual pressure of shift work and occupational stress and may lead to occupational burnout. It not only endangers the physical and mental health of employees, but also threaten the safe and stable operation of the power system. Objective To explore the impact of shift work and occupational stress, as well as their potential interaction, on occupational burnout among employees in power enterprises. Methods From November 2024 to April 2025, cluster sampling was used to select 1378 workers from two power companies in Fuzhou. A self-designed questionnaire, the Effort-Reward Imbalance model, and the Maslach Burnout Inventory were used to investigate the participants’ general information，shift work patterns, occupational stress, and occupational burnout. Statistical analysis was conducted using SPSS 19.0 software. Chi-square test was employed for intergroup comparison. Logistic regression was used to examine the associations between shift work, occupational stress, and job burnout. The multiplicative interaction and additive interaction between shift work and occupational stress on occupational burnout were evaluated. Results A total of 1378 questionnaires were distributed, and 1113 were valid questionnaires, with an effective rate of 80.77%. Among the participants, 37.92% were engaged in shift work, the positive rate of occupational stress was 29.83%, and the positive rate of occupational burnout was 55.80%. The logistic regression analysis showed that after adjusting for confounding factors, the risks of occupational burnout in the non-shift x occupational stress group and the shift x occupational stress group were 1.59 times (95%CI: 1.12, 2.27; P=0.01) and 4.07 times (95%CI: 2.56, 6.45; P<0.01) higher than that in the non-shift x non-occupational stress group. A multiplicative interaction (shift work and occupational stress b=0.75, P=0.01, OR=2.12, 95%CI: 1.18, 3.80) and an additive interaction (relative excess risk ratio=2.24, 95%CI: 0.54, 3.94; attributable fraction=0.55, 95%CI: 0.32, 0.78; interaction index=3.71, 95%CI: 1.47, 9.40) between shift work and occupational stress on job burnout were identified. Conclusion Shift work and occupational stress are risk factors for occupational burnout among employees in power enterprises, and there is a synergistic interaction between these two factors in terms of their impact on occupational burnout.

Cervical spondylotic radiculopathy(CSR)is a condition caused by the degeneration of cervical intervertebral discs and facet joints,primarily manifesting as the pain,sensory abnormalities,and motor dysfunction in the cervical nerve innervation area of neck,shoulder,and upper limb.For the treatment of CSR,tendon-bone syndrome differentiation in traditional Chinese medicine often faces the issues of conceptual confusion and non-standard syndrome differentiation.Based on the traditional tendon-bone syndrome differentiation and by integrating modern anatomical insights,Professor LIN Ding-Kun,an esteemed scholar of Traditional Chinese Medicine,proposed a classification system for the cervical spine that includes the categories of tendons,joints,bones and marrow.This paper explored the thoughts of Professor LIN for the tendon-bone syndrome differentiation of CSR,summarized the targets of manual therapy,and proposed the four kinds of pathological changes such as tendon overstrain,joint dislocation,bone lesion,and marrow injury,as well as the four techniques of traditional Chinese medicine manipulations,i.e.relaxation of tendons,reduction of joints,protection of marrow,and treatment of bones.The aim is to improve the syndrome-differentiation and treatment for CSR with orthopedic and traumatologic manipulations,and to provide reference for clinical practice.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.