OBJECTIVE: To determine risk factors for cutout failure in geriatric intertrochanteric fracture patients after cephalomedullary nail fixation. METHODS: A retrospective review of 518 elderly patients who underwent cephalomedullary nail fixation for intertrochanteric fractures between January 2008 and August 2018 was conducted, including 167 males and 351 females, age from 65 to 97 years old. All patients were followed up for at least one year after surgery and divided into a healed group and a cutout group based on whether the hip screw cutout occurred. Among all patients, 10 cases experienced hip screw cutout. The general information, surgical data, and radiological data of the two groups were compared, and risk factors influencing hip screw cutout were analyzed. Propensity score matching was then performed on the cutout group based on gender, age, body mass index(BMI), and American Society of Anesthesiologists(ASA), and 40 patients from the healed group were matched at a ratio of 1∶4. Key risk factors affecting hip screw cutout were further analyzed. Multivariable logistic regression analysis was conducted to evaluate associations between variables and cutout failure. RESULTS: There were no statistically significant differences between the healed group and the cutout group in terms of age, gender, BMI, ASA, and AO classification. However, statistically significant differences were observed between the two groups in terms of reduction quality(P=0.003) and tip-apex distance(TAD), P<0.001. Multivariate analysis identified poor reduction quality OR=23.138, 95%CI(2.163, 247.551), P=0.009 and TAD≥25 mm OR=30.538, 95%CI(2.935, 317.770), P=0.004 as independent risk factors for cutout failure. CONCLUSION The present study identified poor reduction quality and TAD≥25 mm as factors for cutout failure in geriatric intertrochanteric fractures treated with cephalomedullary nails. Further studies are needed to calculate the optimal TAD for cephalomedullary nails.
Humans ; Male ; Female ; Hip Fractures/surgery* ; Aged, 80 and over ; Aged ; Risk Factors ; Retrospective Studies ; Fracture Fixation, Intramedullary/adverse effects* ; Bone Nails ; Bone Screws

Accurate receptor/ligand binding free energy calculations can greatly accelerate drug discovery by identifying highly potent ligands. By simulating the change from one compound structure to another, the relative binding free energy (RBFE) change can be calculated based on the theoretically rigorous free energy perturbation (FEP) method. However, existing FEP-RBFE approaches may face convergence challenges due to difficulties in simulating non-physical intermediate states, which can lead to increased computational costs to obtain the converged results. To fundamentally overcome these issues and accelerate drug discovery, a new combined-structure RBFE (CS-FEP) calculation strategy was proposed, which solved the existing issues by constructing a new alchemical pathway, smoothed the alchemical transformation, increased the phase-space overlap between adjacent states, and thus significantly increased the convergence and accelerated the relative binding free energy calculations. This method was extensively tested in a practical drug discovery effort by targeting phosphodiesterase-1 (PDE1). Starting from a PDE1 inhibitor (compound 9, IC₅₀ = 16.8 μmol/L), the CS-FEP guided hit-to-lead optimizations resulted in a promising lead (11b and its mesylate salt formulation 11b-Mesylate, IC₅₀ = 7.0 nmol/L), with ∼2400-fold improved inhibitory activity. Further experimental studies revealed that the lead showed reasonable metabolic stability and significant anti-fibrotic effects in vivo.

Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×10⁹/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) μg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.
Child ; Male ; Female ; Humans ; Osteopetrosis/therapy* ; Retrospective Studies ; Prognosis ; Genes, Recessive ; Phosphorus ; Chloride Channels/genetics* ; Vacuolar Proton-Translocating ATPases/genetics*

Objective: To investigate the survival outcomes and prognostic factors of patients with salvage surgery for hypopharyngeal carcinoma after radiotherapy. Methods: A retrospective analysis was performed, including 26 patients treated in Ningbo Medical Center Lihuili Hospital between January 2010 and December 2015. All patients were males, aged 48-83 years, of whom 8 cases were local residual after radiotherapy alone, 8 cases were local recurrence after postoperative radiotherapy, 2 cases were residual of cervical lymph nodes after radiotherapy alone, 2 cases were recurrence of cervical lymph nodes after radiotherapy alone, 2 cases were recurrence of cervical lymph nodes after postoperative radiotherapy and 4 cases were recurrence of tracheal stoma. The salvage operations included: local resection, local resection with neck dissection, simple neck dissection, tumor resection of tracheostomy, and additional repair according to the defect. Chi square test was used for recurrence and metastasis analysis, Kaplan-Meier method for survival analysis, Log-rank test for univariate analysis, and Cox regression model for multivariate analysis. Results: The complication rate of salvage surgery was 23.1% (6/26). The recurrence rate was 65.4% (17/26) and the distant metastasis rate was 42.3% (11/26) in the 5-year follow-up after salvage surgery. Patient's age and tumor invasion extent were correlated with recurrence. Initial treatment, tumor persistence or recurrence after radiotherapy, recurrence location and tumor invasion extent were correlated with distant metastasis (all P<0.05). Overall, 3 year and 5 year survival rates were 42.3% and 23.1% respectively. Age, recurrence location, surgical margin and tumor invasion extent were related to prognosis (χ²=6.56, 10.68, 9.32, and 7.90 respectively, all P<0.05). Multivariate analysis showed that surgical margin and tumor invasion extent were independent risk factors for prognosis (OR (95%CI) = 3.19 (1.03-9.84), 14.37 (2.46-84.08), both P<0.05). Conclusion: Salvage surgery is the first choice for patients with recurrence after radiotherapy for hypopharyngeal carcinoma. Safe surgical margin should be ensured, especially in tumors invading muscle, bone tissue or lymph node capsule.
Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/surgery* ; Humans ; Hypopharyngeal Neoplasms/surgery* ; Male ; Middle Aged ; Neoplasm Recurrence, Local/surgery* ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Salvage Therapy ; Survival Rate

Infertility with diminished ovarian reserve(DOR) is a major problem in the field of reproductive health and it has attracted great attention worldwidely.Function deficiency of the kidney is one of the fundamental pathogenesis for DOR.Traditional Chinese medicines(TCMs) have a long history with rich experience for the treatment of infertility.Some TCMs are very effective in the treatment of kidney deficiency for infertility with DOR.The integrated TCMs and western medicine,and combination of disease differentiation and syndrome differentiation may help for diagnosis and treatment of infertility with DOR.We adopt the concept of unified treatment for special disease,and the methods and principle of treatment can be used.Therefore,we adopt the TCM concept of kidney-tonifying,blood-nourishing,liver-dispersing and spleen-invigorating.The TCMs kidney-tonifying formulae are added and subtracted.TCMs can regulate the reproductive function via multiple systems for simultaneous conditioning of follicular development and ovulation.At the same time,a hypothesis of " simultaneous conditioning of follicular development and ovulation" was proposed.Two-stage therapy with integrated TCMs and western medicine has been used,mainly for increasing the number of eggs,and improving follicle quality.The goal is to achieve simultaneous conditioning of follicular development and ovulation and ultimately for effective treatment of infertility with DOR.

Background: Reverse intertrochanteric fractures are usually initially treated with closed reduction. However, sometimes these fractures are not amenable to closed reduction and require open reduction. To date, few studies have been conducted on predictors of and reduction techniques for irreducible reverse intertrochanteric fractures. Therefore, this study aimed to summarize the displacement patterns of irreducible reverse intertrochanteric fractures and corresponding reduction techniques, and explore predictors of irreducibility. Methods: We reviewed 1174 cases of trochanteric fractures treated in our hospital from January 2006 to October 2018, 113 of which were reverse intertrochanteric fractures. An irreducible fracture was determined according to intra-operative fluoroscopy imaging after closed manipulation. Fractures were assessed for displacement patterns, radiographic features of irreducibility, and reduction techniques. Logistic regression analysis was performed on potential predictors for irreducibility, including gender, age, body mass index, AO Foundation/Orthopaedic Trauma Association (AO/OTA) classification, and radiographic features. Results: Seventy-six irreducible fractures were identified, accounting for 67% of reverse intertrochanteric fractures. Six patterns of fracture displacement after closed manipulation were identified; the most common pattern was medial displacement and posterior sagging of the femoral shaft relative to the head-neck fragment. Multivariate logistic regression analysis identified three predictors of irreducibility: a medially displaced femoral shaft relative to the head-neck fragment on the anteroposterior (AP) view (odds ratio [OR], 8.00; 95% confidence interval [CI], 3.04-21.04; P < 0.001), a displaced lesser trochanter (OR, 3.61; 95% CI, 1.35-9.61; P = 0.010), and a displaced lateral femoral wall (OR, 2.92; 95% CI, 1.02-8.34; P = 0.046). Conclusions A high proportion of reverse intertrochanteric fractures are not amenable to closed reduction. Six patterns of fracture displacement after closed manipulation were identified. Different reduction techniques are required for different displacement patterns. Predictors of irreducibility include a medially displaced femoral shaft relative to the head-neck fragment on the AP view, a displaced lesser trochanter, and a displaced lateral femoral wall. These patients warrant special consideration in terms of recognition and management.

Objective By taking usage of bioinformatics screening methods,this medical research aimed at exploring how the miRNAs in endothelial progenitor cell exosomes relate to the regulation of angiogenesis.Methods miRNAs in endothelial progenitor cells exosomes and angiogenesis-related miRNA was intersected from the existing database to obtain the candidates of miRNA molecules related to angiogenesis in endothelial progenitor exosomes.Results 160 and 50 miRNAs in endothelial progenitor cell candidates were obtained through experimental data analysis and literature searching respectively.600 candidates of angiogenesis-related miRNAs were obtained through literature searching;the top 20 with the highest frequency were selected out.Finally,9 miRNA candidates (miR-126,miR-21,miR-221,miR-92a,miR-199a,miR-210,miR-214,miR-155,miR-146a) that may be highly expressed in endothelial progenitor exosomes and associated with angiogenesis were obtained for the following research.Conclusions Based on data analysis and literature searching,bioinformatics could screen out the target miRNAs for follow-up studies easily and reliably,it is worthy to be widely applied and popularized.

To establish the ultra performance liquid chromatography (UPLC) fingerprint of Dandeng Tongnao Ruanjiaonang and conduct a systemic, comprehensive quality evaluation of the drug by combining with a chemical pattern recognition method. In this study, Waters UPLC ultra-high performance liquid chromatography instrument and ACQUITY UPLCHSS T3 chromatographic colum n were employed to perform the separation with acetonitrile-0.1% formic acid aqueous solution as the mobile phase for gradient elution; and the detection wavelength was set at 256 nm to establish the UPLC fingerprint of 10 batches of Dandeng Tongnao Ruanjiaonang. Then, the further quality assessment of the drug was carried out by similarity evaluation, Cluster Analysis(CA), Principal Component Analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Finally, 77 peaks were recognised as common peaks in the fingerprint, and 15 peaks of them were identified using standard references. The similarity value of these 10 batches of drugs was all above 0.960, indicating a relatively stable quality. But minor differences were still discovered between the batches of the drug by CA and PCA. Finally, 6 common peaks were recognised as the quality makers using OPLS-DA method. The analysis method established in this study was scientific, accurate, reliable and simple; fingerprint combined with chemical pattern recognition technique can be used to systematically and comprehensively evaluate the drug quality of Dandeng Tongnao Ruanjiaonang; what's more, it could also provide a reference for the quality control of traditional Chinese medicine and its preparations at the same time.

An HPLC method was developed for the determination of iridoid glycosides (loganin acid, loganin, sweroside) and saponins (asperosaponin Ⅵ) in the wild Dipsacus asper. A total of 108 samples consecutive growing 12 month were collected in 9 plots in Wulong district of Chongqing. Subsequent analysis of the content of loganin acid, loganin, sweroside and asperosaponin Ⅵ was performed by HPLC to evaluate the quality. In addition, 20 climate data provided by the world climate database (http://www.worldclim.org/) was analyzed to deduce the correlation between the growing environment factors and the active ingredient content accumulation of D. asperoides and choose the apposite growing environment for D. asper. The range of active ingredient content in wild D. asper were 0.01%-3.80%(loganin acid), 0.08%-0.62%(loganin), 0.12%-0.78%(sweroside), 0.64%-5.26%(asperosaponin Ⅵ). The highest content of these active ingredients was concentrated from February to April, with 2.64% of loganin acid, 0.36% of loganin), 0.57% of sweroside, and 3.09% of asperosaponin Ⅵ. The method used for determination of the active ingredient content in D. asper was simple and convenient with accurate result. The selection of the quadrats is scientific and reasonable and can be used for the analysis of the contents of the wild D. asper, thus provide a reference for quality evaluation of D. asper and protection of D. asper resources.

Animals ; Antibodies, Monoclonal ; pharmacokinetics ; therapeutic use ; Antibodies, Viral ; therapeutic use ; Hepatitis B virus ; immunology ; Histocompatibility Antigens Class I ; metabolism ; Humans ; Macaca fascicularis ; Mice ; Protein Binding ; Protein Engineering ; Receptors, Fc ; metabolism