OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective To observe the therapeutic effects of Fourteen-Needle Awakening Acupuncture combined with repetitive transcranial magnetic stimulation(rTMS)on post-stroke patients with minimally conscious state(MCS).Methods Sixty MCS patients admitted to the Rehabilitation Department of Guangdong Second Traditional Chinese Medicine Hospital between December 2023 and December 2024 were randomly divided into an observation group and a control group,with 30 cases in each group.Both groups received conventional awakening therapy.The control group received additional sham rTMS,while the observation group received Fourteen-Needle Awakening Acupuncture combined with rTMS.The treatment duration was 14 days for both groups.After two weeks,awakening status was evaluated.Changes in Coma Recovery Scale-Revised(CRS-R)scores,Glasgow Coma Scale(GCS)scores,Full Outline of Unresponsiveness(FOUR)scores,as well as serum levels of vascular endothelial growth factor(VEGF)and neuron-specific enolase(NSE)were compared between groups before and after treatment.Results(1)After treatment,17 patients in the observation group regained consciousness,with a recovery rate of 56.67％(17/30);9 patients in the control group regained consciousness,with a recovery rate of 30.00％(9/30).The recovery rate in the observation group was significantly higher than that in the control group(P＜0.05).(2)After treatment,the CRS-R scores in both groups were significantly improved(P＜0.05),with the observation group showing a greater degree of improvement(P＜0.05).(3)After treatment,the FOUR scores and GCS scores of both groups were significantly improved(P＜0.05),with the observation group showing a greater degree of improvement(P＜0.05).(4)After treatment,the serum VEGF and NSE levels of both groups were significantly improved(P＜0.05),with the observation group showing a greater degree of improvement(P＜0.05).Conclusion Fourteen-Needle Awakening Acupuncture combined with rTMS effectively enhances cortical excitability and modulates electrophysiological activity of cerebral neurons in post-stroke MCS patients.This combined therapy demonstrates positive therapeutic effects in improving MCS and significantly accelerates consciousness recovery.

AIM To investigate the effects of Congrong San on neuronal apoptosis and the Bax/Bcl-2/Caspase3 signaling pathway in a rat model of Alzheimer's disease(AD).METHODS A total of 60 2-month-old SD male rats were randomly divided into the blank group,the model group,the memantine hydrochloride group(0.025 g/kg)and low-dose,medium-dose and high-dose Congrong San groups(4.62,9.24,18.48 g/kg).All groups except the control group received stereotactic intracerebral injection of Aβ1-42 to establish AD models.Following the successful modeling,each group received its corresponding intragastric administration once daily for 28 consecutive days.After the administration,the rats had their learning and memory ability detected by the morris water maze test;their hippocampal neuronal morphology observed with HE and Nissl staining;their hippocampal neuronal apoptosis observed with TUNEL staining;and their hippocampal expressions of amyloid precursor protein(APP),β-site APP-cleaving enzyme 1(BACE1),and apoptosis-related proteins Bax,Bcl-2 and Caspase3 detected with Western blot assay.RESULTS Compared with the model group,the groups intervened with medium-dose and high-dose Congrong San exhibited improved learning and memory performance,alleviated hippocampal neuronal damage,increased Nissl body count(P＜0.01),reduced hippocampal apoptosis rate(P＜0.05,P＜0.01),decreased protein expressions of APP,BACE1,Bax and cleaved-Caspase3/Caspase3 ratio(P＜0.05,P＜0.01),and elevated Bcl-2 expression(P＜0.01).CONCLUSION Congrong San mitigates cognitive impairment,hippocampal neuronal damage,and apoptosis in AD rats,probably through inhibition of the Bax/Bcl-2/Caspase3 signaling pathway activation.

Objective:To investigate the short-term clinical efficacy of implantation with a 3D-printed microporous titanium prosthesis in the treatment of large segmental infectious tibial defects.Methods:A retrospective analysis was conducted of the electronic medical records of the 47 patients with large segmental tibial defects who had been treated with 3D-printed microporous titanium prostheses at Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force from January 2019 to February 2024. The cohort included 36 males and 11 females, with an age of (46.2±11.8) years and a mean bone defect length of 12.3 (8.0, 16.8) cm. In the 19 patients complicated with soft tissue defects, the area of soft tissue defects ranged from 10.0 cm × 6.0 cm to 33.0 cm × 10.0 cm. For the 28 patients without soft tissue defects at the lower leg, the bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage; for the 19 patients complicated with soft tissue defects, the soft tissue defects at the lower limb were repaired using an anterolateral thigh flap with vascular anastomosis at the same time when bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage. After infection control at 2 to 8 months after surgery, individualized 3D-printed microporous titanium prostheses were implanted at the second stage to reconstruct the bone defects. Postoperative observations included the patients' first standing time, crutch walking time, full weight-bearing time, osseointegration of the tibial fracture and the prosthesis, and complications during follow-up.Results:The follow-up period for the 47 patients was (34.7±14.3) months. The first standing time was (2.2±0.6) months, crutch walking time (3.8±1.1) months, and full weight-bearing time (5.3±1.2) for this cohort. The evaluation by the Paley's bone healing score resulted in 25 excellent cases, 18 good cases, 1 medium case, and 3 poor cases, giving an excellent and good rate of 91.5% (43/47). One year after operation, the X-ray films showed that the tibial fractures and prostheses were well integrated in the 43 patients. Two patients developed recurrent tibial infection which was responded to replacement of the vancomycin-loaded calcium sulfate spacer. The fixation screws for tibial prosthesis were broken in one patient, but no recurrence of infection was observed after revision. The overall incidence of complications was 6.4% (3/47).Conclusion:In the treatment of large segmental infectious tibial defects, by facilitating rapid functional recovery and ensuring a low incidence of complications, implantation with a 3D-printed microporous titanium prosthesis demonstrates fine short-term clinical efficacy.

Objective:To observe any differences in the brain′s functional responses during swallowing with healthy young, middle-aged and elderly individuals.Methods:Fifteen healthy young people formed the youth group, while 15 healthy middle-aged or elderly subjects were the middle-aged and elderly group. Both groups performed repeated swallowing tasks while being observed using functional near-infrared spectroscopy. The data were processed using NirSpark software, and brain activation was compared between the two groups.Results:Swallowing-related brain regions were all significantly activated in the youth group, while in the middle-aged and elderly group only the primary motor cortex (M1), primary somatosensory cortex (PSC), premotor and supplementary motor cortex (pSMC), and inferior central region on the left side showed significantly increased activation. Compared to the youth group, the middle-aged and elderly group exhibited significantly reduced activation in seven channels, including the right M1 and pSMC, the left M1, the pSMC, the PSC, the dorsolateral prefrontal cortex and frontal pole area.Conclusions:The middle-aged and elderly show significantly less activation in certain brain regions during swallowing compared with younger persons. That may be related to aging and its associated cognitive decline, as well as reduced motor and sensory abilities related to swallowing.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective To explore the anatomical landmarks and segmentation method for the intraoperative identification of the cervical segment of the internal carotid artery by studying cadaveric dissections with an endoscopic transoral medial pterygomandibular fold approach and to investigate its clinical significance.Methods The head specimens of five fresh frozen cadavers were dissected in the anatomical laboratory of the Surgical Treatment Technology Innovation Unit of Nasal Skull Base Tumor in Eye&ENT Hospital of Fudan University.The parapharyngeal space was dissected layer by layer through the endoscopic transoral medial pterygomandibular fold approach,and the location marks of parapharyngeal internal carotid artery(ppICA)and adjacent structures of ppICA were anatomically studied.The anatomical landmarks associated with ppICA were observed and characterized,and the ppICA was segmented anatomically according to its adjacent structures.Then,the length of each ppICA segment was measured.Results Muscle structures were essential anatomical landmarks for an endoscopic transoral pterygoid medial approach that identifies mandibular folds.The first layer of muscles included the superior pharyngeal constrictor,tensor veli palatini,and medial pterygoid muscles.The second layer includes the stylopharyngeus,styloglossus,longus capitis,and levator veli palatini muscles.The stylopharyngeal and levator veli palatini muscles were close to the ppICA and were reliable landmarks for locating the ppICA.Furthermore,the ppICA was divided into three segments according to their positional relationship with the ppICA.The first segment of ppICA(P1 ICA)was located between the greater horn plane of the hyoid bone and the intersection plane between the upper margin of stylopharyngeal muscle and ppICA.The second segment of ppICA(P2 ICA)was between the plane where the upper edge of the stylopharyngeal muscle intersected with the ppICA and the plane where the projection of inferior edge of the levator veli palatini muscle intersected with the ppICA.The third segment of ppICA(P3 ICA)was between the intersection of the lower margin projection of the levator veli palatini muscle and ppICA and the external orifice of the carotid canal.The P2 ICA was within an anatomical region bounded by the levator veli palatini muscle,longus capitis muscle,and stylopharyngeus muscle.This region was termed"ICA window"in this paper measured under the cadaver head specimen,the lengths of P1 ICA,P2 ICA,and P3 ICA were(36.5±7.3)mm,(15.5±1.6)mm,(7.4±1.7)mm respectively.Conclusion The muscular structure refers to the relatively constant anatomical reference landmarks within the endoscopic transoral medial pterygomandibular fold.The stylopharyngeus and levator veli palatini muscles are reliable landmarks for precisely locating and segmenting the ppICA,thus having essential clinical implications.

Aim To investigate the effects of Congrong San(CRS)on learning and memory ability,hippocam-pal neuronal injury,and ferroptosis in rats with Alzhei-mer's disease(AD)and to explore the related mecha-nisms.Methods AD rat models were established and divided into Sham,Model,CRS low-dose,CRS medium-dose,CRS high-dose,and memantine groups.After treatment,Morris water maze,HE and Nissl staining,transmission electron microscopy,immunofluorescence staining,Western blot,and kit assays were performed to assess learning and memory ability,hippocampal neuro-nal injury,ferroptosis-related indicatorsand glucose reg-ulated protein 78 ku(GRP78)-(proteinkinaseR-li-keERkinase)PERK-(activating transcription factor 4)ATF4 pathway protein expression.Results Com-pared with the model group,rats in the CRS medium-and high-dose groups and the memantine group showed significant improvement in learning and memory abili-ty,reduced hippocampal neuronal injury,increased number of Nissl bodies,and ameliorated endoplasmic reticulum swelling and mitochondrial damage.In addi-tion,the expressions of GRP78,p-PERK/PERK,and ATF4 were downregulated,while GPX4 expression was upregulated in the CRS medium-and high-dose groups and the memantine group.Moreover,MDA content de-creased,and SOD and GSH-PX levels increased in these groups.Conclusions CRS can improve the learning and memory ability in AD rats,reduce hipp-ocampal neuronal injury and ferroptosis,and its mecha-nism may be related to the inhibition of the GRP78-PERK-ATF4 pathway,enhancement of GPX4 expres-sion,and reduction of oxidative stress levels,providing a new approach for the clinical treatment of AD.