PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95% CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95% CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95% CI: -2.81 - -0.18, p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95% CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95% CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95% CI: -1.64 - -0.52, p = 0.002). CONCLUSION In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.
Humans ; Bone Nails/adverse effects* ; Bone Plates/adverse effects* ; Femoral Fractures/surgery* ; Fracture Fixation, Intramedullary/methods* ; Fractures, Ununited/surgery* ; Lower Extremity/injuries*

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
Humans ; Surgical Wound Infection/epidemiology* ; Male ; Female ; Risk Factors ; Retrospective Studies ; Middle Aged ; Adult ; Case-Control Studies ; Fractures, Bone/surgery* ; Aged ; Drug Resistance, Bacterial ; Logistic Models ; Anti-Bacterial Agents/therapeutic use* ; Incidence ; Bacteria/drug effects*

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:To retrieve, evaluate, and summarize the evidence on fertility management for cervical cancer patients of childbearing age, providing a basis for clinical medical and nursing staff to carry out fertility management for cervical cancer patients.Methods:The evidence on fertility in cervical cancer patients included clinical decision-making, guidelines, summary of evidence, expert consensus, and systematic review, which were systematically searched on domestic and international evidence-based medicine databases, clinical decision-making systems, guideline websites, professional association websites, medical literature service websites, and databases such as UpToDate, Cochrane Library, British Medical Journal (BMJ) Best Practice, China Guidelines Network, China National Knowledge Infrastructure, WanFang Med Online, China Biology Medicine disc, and VIP. The search period was from database establishment to March 1, 2023. Two researchers who received evidence-based nursing knowledge training independently conducted literature screening and quality evaluation, and jointly discussed with clinical experts on the literature that met the requirements to complete evidence extraction and summary.Results:A total of 11 articles were included, including three clinical decision-making, four guidelines, three expert consensus, and one systematic review. A total of 30 pieces of best evidence were summarized from six aspects, including fertility assessment and safety, fertility preservation methods, fertility preservation surgery and anti-tumor treatment, fertility timing, pregnancy management and follow-up, and special treatment for pregnancy with cervical cancer.Conclusions:The evidence on fertility management for cervical cancer patients of childbearing age provides a basis for clinical medical and nursing staff to provide fertility guidance for cervical cancer patients. In clinical application, factors such as patient willingness and condition should be fully considered, and personalized treatment plans should be provided to maximize patient benefits.

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. Renal ischemia-reperfusion injury (RIRI) is one of the main causes of AKI with the underlying mechanism incompletely clarified. The liver X receptors (LXRs), including LXRα and LXRβ, are members of the nuclear receptor superfamily. It has been shown that LXRs play an important role in regulating glucose and lipid metabolism, cholesterol efflux, and inflammation. The purpose of this study was to explore the role and mechanism of LXRs in RIRI. We determined the effects of LXR activation on renal function and histological changes in a mouse RIRI model and a cellular model of hypoxia/reoxygenation (H/R). In vivo results showed that LXRs agonist GW3965 significantly inhibited the increase of serum creatinine and urea nitrogen levels induced by RIRI. Both HE and PAS staining of kidney tissues revealed that GW3965 alleviated the morphological damages caused by RIRI. Immunohistochemical staining showed that GW3965 mitigated 4-HNE and GRP78 levels induced by RIRI. Furthermore, TUNEL assay indicated that GW3965 reduced RIRI-induced renal cell apoptosis. Quantitative real-time PCR (qPCR) analysis revealed that GW3965 attenuated RIRI-induced IL-6 and IL-1β mRNA expression. Compared with wild-type group, LXRα gene deficiency had little effect on RIRI-associated renal functional decline and morphological damages. Additionally, in vitro study demonstrated that GW3965 alleviated H/R-induced decrease of HK-2 human renal proximal tubule cell viability and restored the activity of superoxide dismutase (SOD) after H/R. Western blot results showed that GW3965 mitigated the increase of 4-HNE and GRP78 protein expression levels after H/R; However, knockdown of LXRβ using the small interfering RNA (siRNA) technique reduced cell viability compared to GW3965-treated group. Taken together, the LXRs agonist GW3965 significantly alleviates RIRI in mice possibly by reducing apoptosis, oxidative stress, endoplasmic reticulum stress and inflammation. These results also preliminarily confirm that the renal protective effects of LXRs agonists are dependent on LXRβ.
Animals ; Liver X Receptors/genetics* ; Reperfusion Injury/prevention & control* ; Mice ; Benzoates/pharmacology* ; Benzylamines/pharmacology* ; Male ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Apoptosis ; Acute Kidney Injury/prevention & control* ; Kidney/pathology* ; Humans

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

OBJECTIVE: To establish an intestinal organoid model that mimic acute graft versus host disease (aGVHD) caused intestinal injuries by using aGVHD murine model serum and organoid culture system, and explore the changes of aGVHD intestine in vitro by advantage of organoid technology. METHODS: 20-22 g female C57BL/6 mice and 20-22 g female BALB/c mice were used as donors and recipients for bone marrow transplantation, respectively. Within 4-6 h after receiving a lethal dose (8.0 Gy) of γ ray total body irradiation, a total of 0.25 ml of murine derived bone marrow cells (1×10⁷/mice, n=20) and spleen nucleated cells (5×10⁶/mice, n=20) was infused to establish a mouse model of aGVHD (n=20). The aGVHD mice were anesthetized at the 7th day after transplantation, and the veinal blood was harvested by removing the eyeballs, and the serum was collected by centrifugation. The small intestinal crypts of healthy C57BL/6 mice were harvested and cultivated in 3D culture system that maintaining the growth and proliferation of intestinal stem cells in vitro. In our experiment, 5%, 10%, 20% proportions of aGVHD serum were respectively added into the organoid culture system for 3 days. The formation of small intestinal organoids were observed under an inverted microscope and the morphological characteristics of intestinal organoids in each groups were analyzed. For further evaluation, the aGVHD intestinal organoids were harvested and their pathological changes were observed. Combined with HE staining, intestinal organ morphology evaluation was performed. Combined with Alcian Blue staining, the secretion function of aGVHD intestinal organoids was observed. The distribution and changes of Lgr5⁺ and Clu⁺ intestinal stem cells in intestinal organoids were analyzed under the conditions of 5%, 10% and 20% serum concentrations by immunohistochemical stainings. RESULTS: The results of HE staining showed that the integrity of intestinal organoids in the 5% concentration serum group was better than that in the 10% and 20% groups. The 5% concentration serum group showed the highest number of organoids, the highest germination rate and the lowest pathological score among experimental groups, while the 20% group exhibited severe morphological destruction and almost no germination was observed, and the pathological score was the highest among all groups(t=3.668, 4.334,5.309,P<0.05). The results of Alican blue staining showed that the secretion function of intestinal organoids in serum culture of aGVHD in the 20% group was weaker than that of the 5% group and 10% of the organoids, and there was almost no goblet cells, and mucus was stainned in the 20% aGVHD serum group. The immunohistochemical results showed that the number of Lgr5⁺ cells of intestinal organoids in the 5% group was more than that of the intestinal organoids in the 10% aGVHD serum group and 20% aGVHD serum group. Almost no Clu⁺ cells were observed in the 5% group. The Lgr5⁺ cells in the 20% group were seriously injuried and can not be observed. The proportion of Clu⁺ cells in the 20% group significantly increased. CONCLUSION The concentration of aGVHD serum in the culture system can affect the number and secretion function of intestinal organoids as well as the number of intestinal stem cells in organoids. The higher the serum concentration, the greater the risk of organoid injury, which reveal the characteristics of the formation and functional change of aGVHD intestinal organoids, and provide a novel tool for the study of intestinal injury in aGVHD.
Mice ; Female ; Animals ; Mice, Inbred C57BL ; Bone Marrow Transplantation ; Graft vs Host Disease ; Stem Cells ; Organoids

Objective:To investigate the role of TiRobot combined with O-arm assisted closed reduction and percutaneous screw fixation in unstable pelvic fracture surgery.Methods:Twelve patients with unstable pelvic fractures, 7 males and 5 females, aged 39.41±12.56 years (range 25-60 years), admitted from January 2020 to January 2021, were retrospectively analyzed. The duration between injury and surgery was 9.67±5.81 d (range 4-24 d). The following are the causes of injury, namely traffic injury in 6 cases, fall from height injury in 4 cases, crush injury in 2 cases. Tile type of pelvic fractures were 3 cases of type B (2 cases of type B2, 1 case of type B3), 9 cases of type C (4 cases of type C1, 3 cases of type C2, 2 cases of type C3). Sacral fractures with Denis division were 5 cases of zone I, 7 cases of zone II. Seven patients were repositioned by intraoperative traction on the injured side of the limb and maintained by fixation with a Starr frame. Two cases were repositioned by intraoperative longitudinal bone traction on each lower limb for fracture displacement. The other 3 B-type fractures were repositioned by inserting Schanz nails into the anterior inferior iliac spine bilaterally. Then, the fractures were maintained with external pelvic fixators. The fractures were assessed by O-arm fluoroscopy. Hollow screws were placed with the aid of orthopedic robotic guidance, and the screw positions were verified by O-arm fluoroscopy again after the nail placement. The duration of each screw placement and operation were recorded. The quality of fracture repositioning, hip function and postoperative complications were observed at the follow-up.Results:All patients were followed up for 8.17±1.99 months (range, 6-12 months). There were 27 screws inserted in 12 patients, with a single screw insertion duration of 19.9±1.8 min (range, 9-31 min). In all patients, one O-arm fluoroscopy was performed in each row after closed reduction and after completion of nail placement. The operative duration was 257.78±80.63 min (range, 160-450 min). The O-arm fluoroscopy after nail placement verified that 23 screws were placed in a satisfactory position at one time, with satisfactory rate of 85% (23/27) for the first nail placement. Two patients with preoperative grade II sacral plexus nerve injury recovered to grade I in one case and grade II in one case. However, the numbness was reduced after operation. No further aggravation of nerve injury occurred after surgery. The quality of fracture repositioning was evaluated according to the Matta score, including excellent in 9 cases, good in 2 cases, and acceptable in 1 case, with an excellent rate of 92% (11/12). At the last follow-up, the Majeed pelvic fracture quantitative assessment system scored 85.75±5.82 (range, 74-96). There were 8 cases in excellent and 4 cases in good. Twelve patients had one-stage wound healing. No complications, such as incision infection, nerve injury, loosening and breaking of the internal fixation occurred during the follow-up.Conclusion:TiRobot combined with O-arm assisted closed reduction and percutaneous screw fixation for unstable pelvic fractures has some advantages, including safety, precision, convenient nail placement, and less fluoroscopic radiation.

Objective: To investigate the clinical and pathological features of salivary secretory carcinoma (SSC). Methods: Ten cases of SSC confirmed in the Department of Pathology,Capital Medical University School of Stomatology from January 2014 to December 2021 were retrospectively included, including 5 males and 5 females, with a median age of 46.5 years. The microscopic morphology, immunophenotype, special staining and clinical follow-up of 10 cases of salivary secretory carcinoma were observed. Ten patients were tested with S-100, vimentin, mammaglobin, Dog-1, p63 and Ki-67, 9 cases with cytokeratin (CK) 8/18, 8 with CK7, 6 with calponin, 5 with smooth muscle actin (SMA) and GCDFP15, 4 with CK5/6 and 1 with SOX10. The ETV6-NTRK3 fusion gene was detected by fluorescence in situ hybridization. Results: Seven of the 10 SSC were located in the parotid gland and 3 were located in the cheeks. Histomorphology showed solid, papillary-cystic, follicular, microcystic, and macrocystic types. In 7 cases, tumor cells were dominated by single arrangement type, while certain mixed arrangements existed in some areas. The cytoplasm of the tumor cells was rich in eosinophilic, fine granular or vacuolar shapes, and clear cytoplasm was seen in 2 cases. The nuclei were mostly oval-shaped vesicular nuclei, with nucleoli in the center. Immunohistochemistry showed CK7 (8/8) positive, CK8/18 (9/9) positive, S-100 (10/10) positive, vimentin (5/10) positive, (4/10) partially positive and (1/10) less partially positive, mammaglobin (7/10) positive, (1/10) partially positive and (2/10) some individual cells positive, Dog-1 (10/10) negative, CK5/6 (4/4) negative, p63 (7/10) negative and (3/10) partially positive, SMA (5/5) negative, calponin (6/6) negative, and Ki-67 index was 5%-20%. Secretions of 5 cases showed periodic acid-Schiff (PAS) and PAS with diastase (PAS-D) staining positive. All 10 cases showed ETV6-NTRK3 fusion positive. Six cases were successfully followed up for 32-91 months, of which 2 cases recurred after 28 and 74 months and underwent surgical resection again. All cases followed up are alive and disease-free. Conclusions: The salivary secretory carcinoma is a rare low-grade malignant tumor. In certain cases, morphology is atypical and mammaglobin is immunohistochemically positive in only individual tumor cells. Therefore, the diagnosis should be supported with morphology, immunohistochemical staining, and molecular feature preferably.
Female ; Male ; Biomarkers, Tumor ; Carcinoma/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Neoplasm Recurrence, Local ; Retrospective Studies ; S100 Proteins ; Salivary Gland Neoplasms/pathology* ; Vimentin